Advertisement
Research Article| Volume 1, ISSUE 3, P479-500, September 1981

Antiepileptic Therapeutic Drug Monitoring

  • Stanley L. Cohan
    Correspondence
    Corresponding author: Department of Neurology, Georgetown University Hospital, 3800 Reservoir Road NW, Washington, D.C. 20007
    Affiliations
    Associate Professor, Departments of Neurology and Pharmacology, Georgetown University Hospital, Washington, D.C.
    Search for articles by this author
DOI:https://doi.org/10.1016/S0272-2712(18)31086-2
Antiepileptic Therapeutic Drug Monitoring
Previous ArticleTherapeutic Drug Monitoring: Pharmacokinetic and Pharmacodynamic Principles
Next ArticleAntiarrhythmic Drug Monitoring
      This paper is only available as a PDF. To read, Please Download here.
      The drugs used by many patients with convulsive disorders are readily measured in plasma, and in most cases the plasma concentration is a valid measure of the appropriateness of the drug dose. In the event of a poor therapeutic response, therapeutic monitoring can help to determine if the cause is improper dosage, noncompliance, or the presence of other drugs.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.

      Subscribe:

      Subscribe to Clinics in Laboratory Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Register: Create an account
      Institutional Access: Sign in to ScienceDirect

      References

        • Abraham C.V.
        • Gresham D.
        Simultaneous gas chromatographic analysis for the seven commonly used antiepileptic drugs in serum.
        J. Chromatogr. 1977; 136: 332-336
        • Adams R.F.
        • Schmidt G.J.
        • Vandermark F.L.
        A micro liquid column chromatography procedure for twelve anticonvulsants and some of their metabolites.
        J. Chromatogr. 1978; 145: 275-284
        • Adams R.F.
        • Vandermark F.L.
        Simultaneous high pressure liquid chromatography determination of anticonvulsants in serum.
        Clin. Chem. 1976; 22: 25-31
        • Agarwal P.
        • Blake M.I.
        Determination of the pKa value for 5,5-diphenylhydantoin.
        J. Pharm. Sci. 1968; 57: 1434-1435
        • Albert K.S.
        • Hallmark M.R.
        • Sakmar E.
        • et al.
        Plasma concentrations of diphenylhydantoin, its parahydroxylated metabolite, and corresponding glucuronide in man.
        Res. Commun. Chem. Pathol. Pharmacol. 1974; 9: 463-469
        • Albert K.S.
        • Sakmar E.
        • Hallmark M.R.
        • et al.
        Bioavailability of diphenylhydantoin.
        Clin. Pharmacol. Ther. 1974; 16: 727-735
        • Algieri E.J.
        • McBay A.J.
        Metabolite of phenobarbital in human urine.
        Science. 1956; 23: 183-184
        • Alvin J.D.
        • Bush M.T.
        Physiologic disposition of the anti-convulsants.
        in: Vida J.A. Anticonvulsants. Vol. 15, Medicinal Chemistry—A Series of Monographs. Academic Press, New York1978: 113-151
        • Arnold K.
        • Gerber N.
        The rate of decline of diphenylhydantoin in human plasma.
        Clin. Pharmacol. Ther. 1970; 11: 121-134
        • Atkinson A.J.
        • Shaw J.M.
        Pharmacokinetic study of a patient with diphenylhydantoin toxicity.
        Clin. Pharmacol. Ther. 1973; 14: 521-528
        • Ayers G.J.
        • Goudie J.H.
        • Reed K.
        • et al.
        Quality control in the simultaneous assay of an ticonvulsants using an automated gas chromatographic system with a nitrogen detector.
        Clin. Chim. Acta. 1977; 76: 113-124
        • Baker K.M.
        • Frigerio A.
        • Morselli P.H.
        • et al.
        Identification of a rearranged degradation product from carbamazepine-10,11-epoxide.
        J. Pharmacol. Sei. 1973; 62: 475-476
        • Bardy A.
        • Hari R.
        • Lehtovaara R.
        • et al.
        Valproate may lower serum phenytoin.
        Lancet. 1976; 1: 1297-1298
        • Barnes S.E.
        • Bland D.
        • Cole A.P.
        The use of sodium valproate in a case of status epilepticus.
        Dev. Med. Child. Neurol. 1976; 18: 236-238
        • Bartels H.
        • Oldings H.D.
        • Guther E.
        Use of saliva in monitoring carbamazepine medication in epileptic children.
        Eur. J. Pediatr. 1977; 126: 37-44

      16. Baumei, I. P., Gallagher, B. B., and Mattson, R. H.: Phenylethylmalondiamide (PEMA).

        • Beam R.E.
        Broad-spectrum simultaneous GLC assay of nonderivatized anti-epileptic drugs.
        Am. J. Med. Technol. 1974; 40: 211-218
        • Bochner F.
        • Hooper W.D.
        • Sutherland J.M.
        • et al.
        The renal handling of diphenylhydantoin and 5-(p-hydroxyphenyl)-5-phenylhydantoin.
        J. Pharmacol. Exp. Ther. 1973; 14: 791-796
        • Booker H.E.
        • Hosok K.
        • Burdette R.D.
        • et al.
        A clinical study of serum primidone levels.
        Epilepsia. 1970; 11: 395-402
        • Boque J.Y.
        • Carrington H.C.
        The evaluation of mysoline—A new anticonvulsant drug.
        Br. J. Pharmacol. 1953; 8: 230-235
        • Boque J.Y.
        • Carrington H.C.
        • Bently S.
        L’activite anticonvulsive de la mysoline.
        Acta Neurol. Belg. 1956; 56: 640-645
        • Boreus L.O.
        • Jailing B.
        • Kallberg N.
        Phenobarbital metabolism in adults and in newborn infants.
        Acta Pediatr. Scand. 1978; 67: 193-200
        • Bragmann G.
        • Nolte R.
        Application of a nitrogen-specific detector for the gas chromatographic determination of phenytoin, primidone, and phenobarbitone in 20 μΐ serum.
        in: Schneider H. Clinical Pharmacology of Anti-Epileptic Drugs. Springer-Verlag, Berlin1975: 317-322
        • Brown T.R.
        • Dreifuss F.E.
        • Dyken P.R.
        • et al.
        Ethosuximide in the treatment of absence (petit mal) seizures.
        Neurology (Minneap.). 1975; 25: 515-524
        • Bruni J.
        • Wilder B.J.
        Valproic acid. Review of a new anti-epileptic drug.
        Arch. Neurol. 1979; 36: 393-398
        • Bruni J.
        • Wilder B.J.
        • Willmore L.J.
        • et al.
        Valproic acid and plasma levels of phenytoin.
        Neurology (Minneap.). 1979; 29: 904-905
        • Buchthal F.
        • Svensmark O.
        • Schiller P.J.
        Clinical and electroencephalo graphic correlations with serum levels of diphenylhydantoin.
        Arch. Neurol. 1960; 2: 624-630
        • Butler T.C.
        Metabolic oxidation of phenobarbital to p-hydroxyphenobarbital.
        Science. 1954; 120: 494
        • Butler T.
        The metabolic conversion of 5,5-diphenylhydantoin to 5-(p-hydroxyphenyl)-5-phenylhydantoin.
        Clin. Pharmcol. Ther. 1973; 14: 791-796
        • Butler T.C.
        The metabolic hydroxylation of phenobarbital.
        J. Pharmacol. Exp. Ther. 1956; 116: 326-336
        • Butler T.C.
        • Waddell W.T.
        Metabolic conversion of primidone to phenobarbital.
        Proc. Soc. Exp. Biol. Med. 1956; 93: 544-548
        • Cereghino J.J.
        Serum carbamazepine concentrations and clinical control.
        Adv. Neurol. 1975; 11: 309-330
        • Cereghino J.J.
        • Brock J.C.
        • Van Meter J.E.
        • et al.
        The efficacy of carbamazepine combinations in epilepsy.
        Clin. Pharmacol. Ther. 1975; 18: 733-741
        • Cereghino J.J.
        • Van Meter J.C.
        • Brock J.T.
        • et al.
        Preliminary observations of serum carbamazepine concentration in epileptic patients.
        Neurology (Minneap.). 1973; 23: 357-361
        • Chang T.
        • Dill W.A.
        • Glazko A.J.
        Ethosuximide: Absorption, distribution and excretion.
        in: Woodbury D.M. Antiepileptic Drugs. Raven Press, New York1972: 417-423
        • Chapman C.
        • Kappatos D.
        • Siebers R.W.L.
        Evaluation and comparison of serum phenytoin assay by gas-chromatography and two multiplied immunoassay techniques.
        N.Z.J. Lab. Technol. 1979; 33: 33-36
        • Chen G.
        • Portman R.
        • Ensor C.R.
        • et al.
        Anticonvulsant activity of α-phenyl succinimides.
        J. Pharmacol. Exp. Ther. 1951; 103: 54-61
        • Chen G.
        • Weston J.K.
        • Bratton Jr., A.C.
        Anticonvulsant activity and toxicity of phenosuximide, methsuximide, and ethosuximide.
        Epilepsia. 1963; 4: 66-76
        • Christiansen J.
        • Dam M.
        Drug interaction in epileptic patients.
        in: Schneider H. Clinical Pharmacology of Anti-Epileptic Drugs. Springer-Verlag, Berlin1975: 197-200
        • Christensen L.K.
        • Skousted L.
        Inhibition of drug metabolism by chloramphenicol.
        Lancet. 1969; 2: 1397-1399
        • Cotter L.M.
        • Eadie M.J.
        • Hooper W.D.
        • et al.
        The pharmacokinetics of carbamazepine.
        Eur. J. Clin. Pharmacol. 1977; 12: 451-456
        • Cotter L.M.
        • Smith G.
        • Hooper W.D.
        • et al.
        The bioavailability of carbamazepine.
        Proc. Aust. Assoc. Neurol. 1975; 12: 123-128
        • Craig C.
        • Hirano K.
        • Shideman F.S.
        Anticonvulsant activity of a metabolite of phenobarbital.
        Fed. Proc. 1960; 19: 280
        • Cramers C.A.
        • Vermeer E.A.
        • van Kuik L.G.
        • et al.
        Quantitative determination of underivatized anti-convulsant drugs by high resolution gas chromatography with support-coated open tubular columns.
        Clin. Chim. Acta. 1976; 73: 97-107
        • Cucinell S.A.
        Drug interactions in man. I. Lowering effect of phenobarbital on plasma levels of bishydroxycoumarin (Dicumarol) and diphenylhydantoin (Dilantin).
        Clin. Pharmacol. Ther. 1965; 6: 420-429
        • Darr M.
        • Olesen V.
        Intramuscular administration of phenytoin.
        Neurology (Minneap.). 1966; 16: 288-292
        • De Grave J.
        • Vanro J.
        Simultaneous determination of methylated barbiturates and other anticonvulsant drugs by high-resolution gas chromatography.
        J. Chromatogr. 1976; 129: 171-179
        • Diehl L.W.
        • Muller-Oerlinghauser B.
        • Riedel E.
        The importance of individual pharmacokinetic data for the treatment of epilepsy with carbamazepine.
        Int. J. Clin. Pharmacol. Biopharm. 1976; 14: 144-148
        • Dijkhuis I.C.
        • Vervloet E.
        Rapid determination of the anti-epileptic drug di-n-propylacetric acid in serum.
        Pharma. Weekblad. 1974; 109: 1-4
        • Dill W.A.
        • Kazenko A.
        • Wolf L.M.
        • et al.
        Studies on 5,5-diphenyl-hydantoin (Dilantin) in animals and man.
        J. Pharmacol. Exp. Ther. 1956; 118: 270-279
        • DiSalle E.
        • Pacifici G.M.
        • Morselli P.L.
        Studies on plasma protein binding of carbamazepine.
        Pharmacol. Res. Commun. 1974; 6: 193-202
        • Dudley K.H.
        • Bius D.L.
        • Kraus B.L.
        • et al.
        Gas chromatographic on-column methylation technique for the simultaneous determination of anti-epileptic drugs in blood.
        Epilepsia. 1977; 18: 259-276
        • Dusci L.J.
        • Hackett L.P.
        Gas chromatographic determination of valproic acid in human plasma.
        J. Chromatogr. 1977; 132: 145-147
        • Eadie M.J.
        Laboratory control of anticonvulsant dosage.
        Drugs. 1974; 8: 386-397
        • Eichelbaum M.
        • Bertilsson L.
        • Lund L.
        • et al.
        Plasma levels of carbamazepine-10,11-epoxide during treatment of epilepsy.
        Eur. J. Clin. Pharmacol. 1976; 9: 417-421

      56. Ibid.

      57. Ibid.

        • Eichelbaum M.
        • Ekbom K.
        • Bertilsson L.
        • et al.
        Plasma kinetics of carbamazepine and its epoxide metabolite in man after single and multiple doses.
        Eur. J. Clin. Pharmacol. 1975; 8: 337-341
        • Espir M.L.E.
        • Benton P.
        • Will E.
        Sodium valproate (Epilim): Some clinical and pharamacological aspects.
        in: Legg N.J. Clinical and Pharmacological Aspects of Sodium Valproate (Epilim) in the Treatment of Epilepsy. MCS Consultants, Tunbridge Wells1976: 145-151
        • Eymard P.
        • Simiana J.
        Etude de la repartition et de la resorption du diprophylacetate de sodium marque C chez le rat.
        J. Pharmacol. 1971; 2: 259-268
        • Faigle J.W.
        • Brechbuhler S.
        • Feldman K.F.
        • et al.
        The biotransformation of carbamazepine.
        in: Birkmayer W. Epileptic Seizures-Behavior-Pain. Hans Huber Publishers, Bern1976: 127-140
        • Faigle J.W.
        • Feldmann K.F.
        Pharmacokinetic data of carbamazepine and its major metabolites in man.
        in: Scheinder H. Clinical Pharmacology of Anti-Epileptic Drugs. Springer-Verlag, Berlin1975: 159-165
        • Fernardes B.
        • Eymard P.
        Metabolism of valproate sodium in rabbit, rat, dog, and man.
        Epilepsia. 1977; 18: 169-182
        • Fouts J.R.
        • Hart L.G.
        Hepatic drug metabolism during the perinatal period.
        Ann. N.Y. Acad. Sei. 1965; 123: 245-251
        • Friel P.
        • Troupin A.S.
        Flash-heater ethylation of some anti-epileptic drugs.
        Clin. Chem. 1975; 21: 751-754
        • Frigerio A.
        • Fanelli R.
        • Biandrate P.
        • et al.
        Mass spectrometric characterization of carbamazepine-10,11-epoxide, a carbamazepine metabolite isolated from human urine.
        J. Pharm. Sci. 1972; 61: 1144-1147
        • Fujimoto J.M.
        • Donnelly R.A.
        Effect of feeding and fasting on excretion of phenobarbital in the rabbit.
        Clin. Toxicol. 1968; 1: 297-397
        • Gallagher B.B.
        • Baumei I.P.
        Primidone: Biotransformation.
        in: Woodbury D.M. Antiepileptic Drugs. Raven Press, New York1972: 361-366
        • Gallagher B.B.
        • Baumei I.P.
        • Mattson R.H.
        Metabolic disposition of primidone and its metabolites in epileptic subjects after single and repeated administration.
        Neurology (Minneap.). 1972; 22: 1186-1192
        • Gallagher B.B.
        • Smith D.
        • Mattson R.H.
        The relationship of anticonvulsant properties of primidone to phenobarbital.
        Epilepsia. 1970; 11: 293-301
        • Gardner-Thorpe C.
        • Parsonage M.I.
        • Smethurst P.F.
        • et al.
        A comprehensive gas chromatographic scheme for the estimation of antiepileptic drugs.
        Clin. Chim. Acta. 1972; 36: 223-230
        • Garrettson L.K.
        • Juskp W.J.
        Diphenylhydantoin elimination kinetics in overdosed children.
        Clin. Pharmacol. Ther. 1975; 17: 481-491
        • Garrettson L.K.
        • Perel J.M.
        • Dayton P.G.
        Methylphenidate interaction with both an ticonvulsant and ethyl biscoumacetate.
        J.A.M.A. 1969; 207: 2053-2056
        • Gerardin A.P.
        • Abadie F.V.
        • Campestrini J.A.
        • et al.
        Pharmacokinetics of carbamazepine in normal humans after single and repeated oral doses.
        J. Pharmacokinet. Biopharm. 1976; 4: 521-535
        • Gerardin A.
        • Hirtz J.
        The quantitative assay of carbamazepine in biological material and its application to basic pharmacokinetic studies.
        in: Birkmayer W. Epileptic Seizures-Behavior-Pain. Hans Haber Publishers, Bern1976: 151-164
        • Gerber N.
        • Wagner J.G.
        Explanation of dose-dependent decline of diphenylhydantoin plasma levels by fitting to the integrated form of the Michaelis-Menten equation.
        Res. Commun. Chem. Pathol. Pharmacol. 1972; 3: 455-466
        • Giovanniello T.J.
        • Pecci J.
        Simultaneous isothermal determination of diphenylhydantoin and phenobarbital serum levels by gas-liquid chromatography following flash-heater hexylation.
        Clin. Chim. Acta. 1976; 67: 7-13
        • Glazko A.
        Antiepileptic drugs: Biotransformation, metabolism, and serum halflife.
        Epilepsia. 1975; 16: 367-391
        • Glazko A.J.
        Diphenylhydantoin—Chemistry and methods for determination.
        in: Woodbury D.M. Antiepileptic Drugs. Rayen Press, New York1972: 103-112
        • Glazko A.J.
        Diphenylhydantoin metabolism: A prospective review.
        Drug Metab. Dispos. 1973; 1: 711-714
        • Glazko A.J.
        • Chang T.
        Diphenylhydantoin—Absorption, distribution, and excretion.
        in: Woodburg D.M. Antiepileptic Drugs. Raven Press, New York1972: 103-112
        • Glazko A.J.
        • Dill W.A.
        • Drach J.C.
        • et al.
        Biological availability of drugs: Evaluation from blood level and urinary excretion data.
        Fifth National Meeting Acad. Pharm. Sci., Washington, D.C.1970: 326-343
        • Godin Y.
        • Heiner L.
        • Mark J.
        • et al.
        Effects of di-n-propylacetate, an anticonvulsant compound, on GABA metabolism.
        J. Neurochem. 1969; 16: 869-873
        • Godolphin W.
        • Thoma J.J.
        Quantitation of anticonvulsant drugs in serum by gas chromatography on the station phase SP-25.
        Clin. Chem. 1978; 24: 483-485
        • Gruber C.M.
        • Mosier J.M.
        • Grant P.
        Objective comparison of primidone and phenobarbital in epileptics.
        J. Pharm. Exp. Ther. 1957; 120: 184-187
        • Goldensohn E.S.
        • Hardie J.
        • Borea E.
        Ethosuximide in the treatment of epilepsy.
        J.A.M.A. 1962; 180: 840-942
        • Goudie J.H.
        • Burnett D.
        A gas-chromatographic method for the simultaneous determination of phenobarbitone, primidone and phenytoin in serum using a nitrogen detector.
        Clin. Chim. Acta. 1973; 43: 423-429
        • Gram L.
        • Flachs H.
        • Wartz-Horgansen A.
        • et al.
        Valproate, serum levels and clinical effect in epilepsy: A controlled study.
        Epilepsia. 1979; 20: 303-312
        • Gram L.
        • Walff K.
        • Rasmussen K.E.
        Valproate sodium: A controlled clinical trial in cluding monitoring of drug levels.
        Epilepsia. 1977; 18: 141-148
        • Guberman A.
        • Gloor P.
        • Sherwin A.L.
        Response of a generalized penicillin epilepsy in the cat to ethosuximide and diphenylhydantoin.
        Neurology (Minneap.). 1975; 25: 758-764

      91. Ibid.

        • Gugler R.
        • Marion C.V.
        • Azarnoff D.L.
        Phenytoin: Pharmacokinetics and bioavailability.
        Clin. Pharmacol. Ther. 1976; 19: 135-142
        • Gyllenhaal O.
        • Brotell H.
        • Sandgren B.
        Determination of phenobarbital in human saliva by gas chromatography with electron-capture detection.
        J. Chromatog. 1976; 122: 471-477
        • Handley R.
        • Stewart A.S.R.
        Mysoline: A new drug in the treatment of epilepsy.
        Lancet. 1952; 1: 742-744
        • Hansen J.M.
        Dicoumarol-induced diphenylhydantoin intoxication.
        Lancet. 1966; 2: 265-266
        • Hansen J.M.
        • Kristensen M.
        • Skovsted L.
        Sulthiame (Ospolot) as inhibitor of diphenylhydantoin metabolism.
        Epilepsia. 1968; 9: 17-22
        • Hansen J.M.
        • Siersbaek-Nielseri K.
        • Skovsted L.
        Carbamazepine induced acceleration of diphenylhydantoin and warfarin metabolism in man.
        Clin. Pharmacol. Ther. 1971; 12: 539-543
        • Harvey C.D.
        • Sherwin A.L.
        • van der Kleijn E.
        Distribution of anticonvulsant drugs in gray and white matter of the human brain.
        Can. J. Neurol. Sei. 1977; 4: 89-92
        • Harvey D.J.
        • Glazener L.
        • Stratton C.
        • et al.
        Detection of a 5-(3,4-dihydroxy-1,5-cyclohex-adine-1-yl) metabolite of phenobarbital and mephobarbital in rat, guinea pig and human.
        Res. Commun. Chem. Pathol. Pharmacol. 1972; 3: 557-565
        • Harvey P.K.P.
        Some aspects of the neurochemistry of Epilim.
        in: Legg N.J. Clinical and Pharmacological Aspects of Sodium Valproate (Epilim) in the Treatment of Epilepsy. MSC Consultants, Tunbridge Wells1976: 130-135
        • Hauptmann A.
        Luninal bei epilepsie.
        Muchn. Med. Wochenschr. 1912; 59: 1907-1909
        • Heipertz R.
        • Pilz H.
        • Eickhoff K.
        Evaluation of a rapid gas chromatographic method for the simultaneous quantitative determination of ethosuxmide, phenyl-ethylmalonamide, carbamazepine, phenobarbital, primidone, and diphenylhydantoin in human serum.
        Clin. Chim. Acta. 1977; 77: 307-316
        • Hershey A.E.
        • Patton J.R.
        • Dudley K.H.
        Gas chromatographic method for the determination of valproic acid in human plasma.
        Ther. Drug Monitor. 1979; 1: 217-241
        • Hooper W.D.
        • Dubetz D.K.
        • Bochner F.
        • et al.
        Plasma protein binding of carbamazepine.
        Clin. Pharmacol. Ther. 1975; 17: 433-440
        • Hooper W.D.
        • Dubetz D.K.
        • Eadie M.J.
        • et al.
        Simultaneous assay of methylphenobarbitone and phenobarbitone using gas-liquid chromatography with on-column butylation.
        J. Chromatogr. 1975; 110: 206-209
        • Horning M.G.
        • Butler C.M.
        • Lertratanangkoon K.
        • et al.
        Gas chromatography-mass spectrometry-computer studies of the metabolism of anticonvulsant drugs.
        in: Kellaway P. Petersen I. Quantitative Analytic Studies in Epilepsy. Raven Press, New York1976: 95-114
        • Horning E.C.
        • Horning M.G.
        Metabolic profiles: Gas-phase methods for analysis of metabolites.
        Clin. Chem. 1971; 17: 802-809
        • Houghton G.W.
        • Richens A.
        • Toseland P.A.
        • et al.
        Brain concentrations of phenytoin, phenobarbital, and primidone in epileptic patients.
        Eur. J. Clin. Pharmacol. 1975; 9: 73-78
        • Jailing B.
        Plasma and cerebrospinal fluid concentrations of phenobarbital in infants given single doses.
        Dev. Med. Child. Neurol. 1968; 10: 626-632
        • Jeavons P.M.
        • Clark J.E.
        • Maheshweri M.C.
        Treatment of generalized epilepsies of childhood and adolescence with sodium valproate (Epilim).
        Dev. Med. Child. Neurol. 1977; 19: 9-26
        • Jensen C.J.
        • Gugler R.
        Sensitive gas-liquid chromatographic method for determination of valproic acid in biological fluids.
        J. Chromatog. 1977; 137: 188-193
        • Johannessen S.I.
        • Gerna M.
        • Bakke J.
        • et al.
        CSF concentrations and serum protein binding of carbamazepine and carbamazepine-10,11-epoxide in epileptic patients.
        Br. J. Clin. Pharmacol. 1976; 3: 575-582
        • Johannessen S.I.
        • Strandjord R.E.
        Concentration of carbamazepine (Tegretol) in serum and in cerebrospinal fluid in patients with epilepsy.
        Epilepsia. 1973; 14: 373-379
        • Kabra P.M.
        • McDonald D.M.
        • Marton L.J.
        A simultaneous high-pressure liquid chromatographic analysis of the most common anticonvulsants and their metabolites in serum.
        J. Anal. Toxicol. 1979; 2: 127-133
        • Kabra P.M.
        • Stafford B.E.
        • Marton L.J.
        Simultaneous measurement of phenobarbital, phenytoin, primidone, and carbamazepine in serum by high pressure liquid chromatography.
        Clin. Chem. 1977; 23: 1284-1288
        • Kauko K.
        • Tammisto P.
        Comparison of two generically equivalent carbamazepine preparations.
        Ann. Clin. Res. 1974; 6: 21-25
        • Kelly R.Č.
        • Valentour J.C.
        • Sunshine I.
        Solvent suppression of the decomposition of phenobarbital during on-column methylation with trimethylanilinium hydroxide.
        J. Chromatogr. 1977; 138: 413-422
        • Kiorboe E.
        Phenytoin intoxication during treatment with Antabuse (disulfiram).
        Epilepsia. 1966; 7: 246-249
        • Klotz U.
        • Antonia K.H.
        Pharmacokinetics and biovailability of sodium valproate.
        Clin. Pharmacol. Ther. 1977; 21: 736-743
        • Kuhara T.
        • Matsumto I.
        Omega oxidation of sodium dipropylacetate: An anticonvulsant drug in rats.
        Res. Biochem. Metab. Pharmacol. 1974; 2: 1382
        • Kupferberg H.J.
        Gas-liquid chromatographic quantitation of valproic acid.
        in: Pippenger C.E. Antiepileptic Drugs: Quantitative Analysis and Interpretation. Raven Press, New York1978: 147-151
        • Kutt H.
        Biochemical and genetic factors regulating Dilantin metabolism in man.
        Ann. N.Y. Acad. Sei. 1971; 179: 704-722
        • Kutt H.
        Diphenylhydantoin intoxication: A complication of isoniazid therapy.
        Am. Rev. Respir. Dis. 1970; 101: 377-384
        • Kutt H.
        • Louis S.
        • McDowell F.
        Intravenous diphenylhydantoin in experimental seizures. I. Correlation of dose, blood and tissue level in cats.
        Arch. Neurol. 1968; 18: 465-471
        • Kutt H.
        • Penry J.K.
        Usefulness of blood levels of antiepileptic drugs.
        Arch. Neurol. 1974; 3Z: 283-288

      126. Ibid.

        • Least C.J.
        • Johnson G.F.
        • Soloman H.M.
        Micro-scale anticonvulsant assay with use of nitrogen/phosphorus detector and on-column methylation compared with a macro-scale procedure involving flame-ionization detection.
        Clin. Chem. 1977; 23: 593-595
        • Lehane D.P.
        • Menyharth P.
        • Lum G.
        • et al.
        Therapeutic drug monitoring: Measurement of anti-epileptic and barbiturate drug levels in blood by gas chromatography with nitrogen selective detector.
        Ann. Clin. Lab. Sei. 1976; 6: 404-410
        • Levy R.H.
        Antiepileptic drugs. Phenytoin: Biopharmacology.
        in: Glaser G.H. Antiepileptic Drugs: Mechanisms of Action. Raven Press, New York1980: 315-321
        • Levy R.H.
        • Lockhard J.S.
        • Green J.R.
        • et al.
        Pharmocokinetics of carbamazepine in monkeys following intravenous and oral administration.
        J. Pharm. Sci. 1975; 64: 302-307
        • Levy R.H.
        • Pitlick W.H.
        • Troupin A.S.
        • et al.
        Pharmacokinetics of carbamazepine in normal man.
        Clin. Pharmacol. Ther. 1975; 17: 657-668
        • Livingston S.
        • Pauli L.
        • Najambadi A.
        Ethosuximide in the treatment of epilepsy.
        J.A.M.A. 1962; 180: 822-825
        • Löscher W.
        Rapid determination of valproate sodium in serum by gas-liquid chromatography.
        Epilepsia. 1977; 18: 225-227
        • Louis S.
        • Kutt H.
        • McDowell F.
        Intravenous diphenylhydantoin in experimental seizures. II. Effect of penicillin-induced seizures in the cat.
        Arch. Neurol. 1968; 18: 472-477
        • Löscher W.
        • Gobel W.
        Consecutive gas chromatographic determination of phenytoin, phenobarbital, primidone, phenylethylamalondiamide, carbamazepine, trimethadione, di-methadione, ethosuximide, and valproate from the same serum specimen.
        Epilepsia. 1978; 19: 463-473
        • Lous P.
        Plasma levels and urinary excretion of three barbituric acids after oral administration to man.
        Acta Pharmacol. Toxicol. 1954; 10: 147-165
        • Lund L.
        Anticonvulsant effect of diphenylhydantoin relative to plasma levels.
        Arch. Neurol. 1974; 31: 289-294
        • Limd L.
        • Alvan G.
        • Berlin A.
        • et al.
        Pharmacokinetics of single and multiple doses of phenytoin in man.
        Eur. J. Clin. Pharmacol. 1974; 7: 81-86
        • Lund L.
        • Berlin A.
        • Lunde P.K.M.
        Plasma protein binding of diphenylhydantoin in patients with epilepsy.
        Clin. Pharmacol. Ther. 1972; 13: 196-200
        • Lunde P.K.M.
        • Rane A.
        • Yaff S.J.
        Plasma protein binding of diphenylhydantoin in man.
        Clin. Pharmacol. Ther. 1970; 11: 846-855
        • Martis L.
        • Levy R.H.
        Bioavailability calculations for drugs showing simultaneous first-order and capacity-limited elimination kinetics.
        J. Pharmacokinet. Biopharm. 1973; 1: 283-294
        • Maynert E.W.
        Phenobarbital, mephobarbital, and metharbital. Absorption, distribution, and excretion.
        in: Woodberry D.M. Antiepileptic Drugs. Raven Press, New York1972: 303-310
        • Maynert E.W.
        Phenobarbital, mephobarbital, and metharbital. Biotransformation.
        in: Woodberry D.M. Antiepileptic Drugs. Raven Press, New York1972: 311-317
        • McAuliffe J.J.
        • Sherwin A.L.
        • Leppik J.E.
        • et al.
        Salivary levels of anticonvulsants: A practical approach to drug monitoring.
        Neurology (Minneap.). 1977; 27: 409-413
        • Meinardi H.
        Clinical trials on anti-epileptic drugs.
        Psychiatr. Neurol. Neurochir. 1971; 74: 141-151
        • Meinardi H.
        • Heuke N.F.J.
        • van Bevern J.
        Sodium-di-n-propylacetate: Estimation of effective serum levels.
        Pharma. Weekblad. 1974; 109: 45-47
        • Meinardi H.
        • van der Kleijn E.
        • Meijer J.W.A.
        • et al.
        Absorption and distribution of antiepileptic drugs.
        Epilepsia. 1975; 16: 353-365
        • Menyharth P.
        • Levy A.L.
        • Lehane D.P.
        Routine therapeutic drug-monitoring using the Perkin-Elmer Mark II gas chromatography fitted with a nitrogen-selective detectro.
        Chromatogr. Newsletter. 1976; 4: 15-19
        • Meunier H.
        • Carraz G.
        • Menunier Y.
        • et al.
        Properties pharmacodynamiques de l’acid n-dipropylacetique. I. Propriete’s antiepileptiques.
        Therapie. 1963; 18: 435-438
        • Miyamoto K.
        • Seino M.
        • Ikeda Y.
        Consecutive determination of the levels of twelve anti-epileptic drugs in blood and cerebrospinal fluid.
        in: Schneider H. Clinical Pharmacology of Anti-Epileptic Drugs. Springer-Verlag, Berlin1975: 323-330
        • Monacco F.
        • Riccio A.
        • Benna P.
        • et al.
        Further observations on carbamazepine plasma levels in epileptic patients.
        Neurology (Minneap.). 1976; 26: 963-973
        • Morselli P.L.
        • Barazzi A.
        • Gerna M.
        • et al.
        Carbamazepine and carbamazepine-10,11-epoxide concentrations in human brain.
        Br. J. Clin. Pharmacol. 1977; 4: 535-540
        • Morselli P.L.
        • Bossi L.
        • Gerna M.
        Pharmacokinetic studies with carbamazepine in epileptic patients.
        in: Birkmayer W. Epileptic Seizures-Behavior-Pain. Hans Huber Publishers, Bern1976: 141-150
        • Morselli P.L.
        • Gerna M.
        • de Maio D.
        • et al.
        Pharmacokinetic studies on carbamazepine in volunteers and in epileptic patients.
        in: Schneider H. Clinical Pharmacology of Anti-Epileptic Drugs. Springer-Verlag, Berlin1975: 166-180
        • Morselli P.L.
        • Monacco F.
        • Gerna M.
        • et al.
        Bioavailability of two carbamazepine preparations during chronic administration to epileptic patients.
        Epilepsia. 1975; 16: 759-764
        • Monacco F.
        • Riccio A.
        • Benna P.
        • et al.
        Further observations on carbamazepine plasma levels in epileptic patients.
        Neurology (Minneap.). 1976; 26: 963-973
        • Nandedkar A.K.N.
        • Gimblet E.
        • Kutt H.
        • et al.
        An evaluation of EMIT reagent system for determination of phenobarbital and phenytoin in du Pont Automatic Clinical Analyzer.
        Clin. Chem. 1979; 25: 1096
        • Nandedkar A.K.N.
        • Kutt H.
        • Fairclough G.F.
        Correlation of EMIT with a gas-liquid chromatographic method for determination of antiepileptic drugs in plasma.
        Clin. Toxicol. 1978; 12: 483-494
        • Nandedkar A.K.N.
        • Williamson R.
        • Kutt H.
        • et al.
        A comparison of plasma phenytoin level determinations by EMIT and gas-liquid chromatography in patients with renal insufficiency.
        Ther. Drug Monitor. 1980; 2: 427-430
        • Norton P.R.E.
        The effects of drugs on barbiturate withdrawal convulsions in rat.
        J. Pharmacol. 1970; 22: 763-766
        • O’Donohoe N.V.
        Treatment of petit mal with ethosuximide.
        Dev. Med. Child. Neurol. 1964; 6: 498-501
        • Olesen O.V.
        Disulfiran (Antabuse) as inhibitor of phenytoin metabolism.
        Acta Pharmacol. Toxicol. 1966; 24: 317-322
        • Olesen O.V.
        • Dam M.
        The metabolic conversion of primidone to phenobarbitone in patients under long-term treatment.
        Acta Neurol. Scand. 1967; 43: 346-351
        • Palmer L.
        • Bertilsson L.
        • Collste P.
        • et al.
        Quantitative determination of carbamazepine in plasma by mass fragmentography.
        Clin. Pharmacol. Ther. 1974; 14: 827-832
        • Patsalos P.N.
        • Lascelles P.T.
        Valproate may lower serum phenytoin.
        Lancet. 1971; 1: 50-51
        • Patton J.R.
        • Hershey A.E.
        • Bius D.L.
        • et al.
        Integrated method for the gas chromatographic determination of anti-epileptic drugs in human plasma.
        Ther. Drug Monitor. 1980; 2: 397-409
        • Penry J.K.
        • Newmark M.E.
        The use of antiepileptic drugs.
        Ann. Intern. Med. 1979; 90: 207-218
        • Penry J.K.
        • Porter R.J.
        • Dreifuss F.E.
        Ethosuximide: Relation of plasma levels to clinical control.
        in: Woodbury D.M. Antiepileptic Drugs. Raven Press, New York1972: 431-441
        • Pesh-Imam M.
        • Fretthold D.W.
        • Sunshine I.
        • et al.
        High pressure liquid chromatography for simultaneous analysis of anticonvulsants: Comparison with EMIT system.
        Ther. Drug Monitor. 1979; 1: 289-299
        • Perucca E.
        • Gatti G.
        • Frigo G.M.
        • et al.
        Disposition of valproate in epileptic patients.
        Br. J. Clin. Pharmacol. 1978; 5: 495-499
        • Pinder R.M.
        • Brodger R.N.
        • Speight T.M.
        Sodium valproate: A review of its pharmacological properties and therapeutic efficacy in epilepsy.
        Drugs. 1977; 13: 81-123
        • Pynnonen S.
        The pharmacokinetics of carbamazepine in plasma and saliva of man.
        Acta Pharmacol. Toxicol. 1977; 41: 465-471
        • Pynnonen S.
        Pharmacokinetics of carbamazepine in man: A review.
        Ther. Drug Monitor. 1979; 1: 409-431
        • Pynnonen S.
        • Kanto J.
        • Sillanpaa M.
        • et al.
        Placental transport tissue concentrations in foetus and newborn, and levels in milk.
        Acta Pharmacol. Toxicol. 1977; 41: 244-253
        • Pynnonen S.
        • Manyla R.
        • Iisalo E.
        Bioavailability of four different pharmaceutical preparations of carbamazepine.
        Acta Pharmacol. Toxicol. 1978; 43: 306-310
        • Pynnonen S.
        • Siirtola T.
        • Molsa P.
        • et al.
        On the distribution of carbamazepine in blood, plasma, saliva, cerebrospinal fluid, and plasma water.
        Acta Neurol. Scand. (Suppl.). 1978; 67: 266-267
        • Pynnonen S.
        • Sillanpaa M.
        Carbamazepine and mother’s milk.
        Lancet. 1975; 2: 563
        • Pynnonen S.
        • Sillanpaa M.
        • Frey H.
        • et al.
        Carbamazepine and its 10,11-epoxide in children and adults with epilepsy.
        Eur. J. Clin. Pharmacol. 1977; 11: 129-133
        • Pynnonen S.
        • Sillanpaa M.
        • Iisalo E.
        • et al.
        Elimination of carbamazepine in children after single and multiple doses.
        in: Penry K. Epilepsy. Raven Press, New York1977: 191-197
        • Rambeck B.
        • Meijer W.A.
        Gas chromatographic methods for the determination of an tiepileptic drugs: A systematic review.
        Ther. Drug Monitor. 1980; 2: 385-396
        • Rane A.
        • Bertilsson L.
        • Palmer L.
        Disposition of placentally transferred carbamazepine (Tegretol) in the newborn.
        Eur. J. Clin. Pharmacol. 1975; 8: 283-284
        • Reidenberg M.M.
        • Odar-Cederlof I.
        • Bahn C.
        Protein binding of diphenylhydantoin and desmethylimipramine in plasma from patients with poor renal function.
        N. Engl. J. Med. 1971; 285: 264-267
        • Richens A.
        • Dunlop A.
        Serum phenytoin levels in the management of epilepsy.
        Lancet. 1975; 2: 247-248
        • Roseman E.
        Dilantin toxicity: A clinical and electroencephalographic study.
        Neurology. 1961; 11: 912-921
        • Rowan A.J.
        • Binnie C.D.
        • de Beer-Pawlikowski N.K.B.
        • et al.
        24-hour EEG studies with very frequent serum antiepileptic drug concentration determinations in the study of valproate.
        in: Meinhardi H. Rowan A.J. Advances in Epileptology—1977. Swets and Zeitlinger, Amsterdam1978: 255-260
        • Schaal D.E.
        • McKinley S.L.
        • Chitwood G.W.
        Gas-liquid gas chromatographic analysis of underivatized anticonvulsants on the stations phase DC-LSX-3-0295.
        J. Anal. Toxicol. 1979; 3: 96-98
        • Schafer H.
        • Luhrs R.
        Metabolite pattern of valproate.
        Arzneim. Forsch. 1978; 28: 657-662
        • Schmidt D.
        • Janz D.
        Therapeutic plasma concentrations of phenytoin and phenobarbitone.
        in: Gardner-Thorpe C. Antiepileptic Drug Monitoring. Pitman Medical, Tunbridge Wells (Kent)1977: 214-225
        • Schneider H.
        Carbamazepine: An attempt to correlate serum levels with antiepileptic and side-effects.
        in: Schneider H. Clinical Pharmacology of Anti-Epileptic Drugs. Springer-Verlag, Berlin1975: 151-158
        • Schobben F.
        • van der Kleijn E.
        Determination of sodium di-n-propylacetate in plasma by gas-liquid chromatography.
        Pharma. Weekblad. 1974; 109: 30-33
        • Schobben F.
        • van der Kleijn E.
        • Gabreels F.
        Pharmacokinetics of di-n-propylacetate in epileptic patients.
        Eur. J. Clin Pharmacol. 1975; 8: 97-105
        • Shobben F.
        • Vree T.B.
        • van der Kleijn E.
        Pharmacokinetics, metabolism, and distribution of 2-n-propyl-pentanoate (valproate) and the influence of salicylate comedication.
        in: Meinardi H. Rowan A.J. Advances in Epileptology—1977. Swets and Zeitlinger, Amsterdam1978: 271-277
        • Schobben F.
        • van der Kleijn E.
        • Vree T.B.
        Therapeutic monitoring of valproic acid.
        Ther. Drug Monitor. 1980; 2: 61-71
        • Schwartz P.A.
        • Rhodes C.T.
        • Cooper Jr., J.W.
        Solubility and ionization characterizations of phenytoin.
        J. Pharm. Sci. 1977; 66: 994-997
        • Schwertner H.A.
        • Hamilton H.E.
        • Wallace J.E.
        Analysis for carbamazepine in serum by electron-capture gas chromatography.
        Clin. Chem. 1978; 24: 895-899
        • Sengupta A.
        • Peat M.A.
        Gas-liquid chromatography of eight anticonvulsant drugs in plasma.
        J. Chromatogr. 1977; 137: 206-209
        • Serrano E.E.
        • Roye D.B.
        • Hammer R.H.
        • et al.
        Plasma diphenylhydantoin values after oral and intramuscular administration of diphenylhydantoin.
        Neurology (Minneap.). 1973; 23: 311-317
        • Sheehan M.
        • Beam R.E.
        GLC determination of underivatized carbamazepine in whole blood.
        J. Pharm. Sci. 1975; 64: 2004-2006
        • Sherwin A.L.
        • Eisen A.A.
        • Sokolowski D.D.
        Anticonvulsant drugs in human epileptogenic brain.
        Arch. Neurol. 1973; 29: 73-77
        • Sherwin A.L.
        • Robb J.P.
        Ethosuximide: Relation of plasma levels to clinical control.
        in: Woodbury D.M. Antiepileptic Drugs. Raven Press, New York1972: 443-448
        • Sherwin A.L.
        • Robb J.P.
        • Lechter M.
        Improved control of epilepsy by monitoring plasma ethosuximide.
        Arch. Neurol. 1973; 28: 178-181
        • Sherwin A.L.
        • Rob J.P.
        Ethosuximide: Relation to plasma levels to clinical control.
        in: Woodburg D.M. Antiepileptic Drugs. Raven Press, New York1972: 443-448
        • Solomon H.M.
        • Schrogie J.J.
        The effect of phenyramidol on the metabolism of diphenylhydantoin.
        Clin. Pharmacol. Ther. 1967; 8: 554-556
        • Solow E.B.
        • Metaxas J.M.
        • Summers T.R.
        Anti-epileptic drugs: A current assessment of simultaneous determination of multiple drug therapy by gas-liquid chromatography on-column methylation.
        J. Chromatogr. Sei. 1974; 21: 256-260
        • Sotel L.
        Experimental antiepileptic action and clinical action of Zarontin.
        Acta Neurol. Psychiatr. Belg. 1960; 60: 551-559
        • Stella V.J.
        Use of trimethylanilinium hydroxide-tetramethylanilinium hydroxide as on-column methylating agent for GLC analysis of phenytoin.
        J. Pharm. Sci. 1977; 66: 1510-1511
        • Strandjord R.E.
        • Johannessen S.J.
        A preliminary study of serum carbamazepine levels in healthy subjects and in patients with epilepsy.
        in: Schneider H. Clinical Pharmacology of Anti-Epileptic Drugs. Springer-Verlag, Berlin1975: 181-188
        • Strandjord R.E.
        • Johannessen S.I.
        Serum levels of phenobarbitone in healthy subjects and patients with epilepsy.
        in: Gardner-Thorpe C. Antiepileptic Drug Monitoring. Pitman Medical, Tunbridge Wells (Kent)1977: 89-103
        • Sutton G.
        • Kupferberg J.H.
        Isoniazid as an inhibitor of primidone metabolism.
        Neurology. 1975; 25: 1179-1181
        • Suzuki M.
        • Marayama H.
        • Ishibashi Y.
        A double-blind comparative trial of sodium dipropylacetate and ethosuximide in epilepsy in children: With special emphasis on pure petit-mal seizures (from English abstract).
        Med. Prog. 1972; 82: 470-488
        • Svensmark O.
        • Buchthal F.
        Accumulation of phenobarbital in man.
        Epilepsia. 1963; 4: 199-206
        • Svensmark O.
        • Schiller P.J.
        • Buchthal F.
        5,5-diphenylhydantoin (Dilantin) blood levels after oral and intravenous dosage in man.
        Acta Pharmacol. 1960; 16: 331-346
        • Thoma J.J.
        • Ewald T.
        • McCoy M.
        Simultaneous analysis of underivatized phenobarbital, carbamazepine, primidone, and phenytoin by isothermal gas-liquid chromatography.
        J. Anal. Toxicol. 1978; 2: 219-225
        • Toseland P.A.
        • Albani M.
        • Gauchei F.D.
        Organic nitrogen-selective detector used in gas-chromatographic determination of some anticonvulsant and barbiturate drugs in plasma and tissues.
        Clin. Chem. 1975; 21: 98-103
        • Trolle E.
        Drug therapy of epilepsy.
        Acta Psychiatr. Scand. (Suppl. 150). 1961; 36: 187-199
        • Troupin A.M.
        • Friel P.
        Anticonvulsant level in saliva, serum and cerebrospinal fluid.
        Epilepsia. 1975; 16: 223-227
        • Troupin A.S.
        • Green J.R.
        • Halpern L.M.
        Carbamazepine (Tegretol) as an anticonvulsant. A controlled double blind comparison with diphenylhydantoin (Dilantin).
        Acta Neurol. Scand. (Suppl.). 1975; 760: 13-26
        • Vajda F.J.E.
        • Drummer O.H.
        • Morris P.M.
        • et al.
        Gas chromatography measurement of plasma levels of valproate. Tentative therapeutic range of a new anticonvulsant in the treatment of refractory epileptics.
        Clin. Exp. Pharmacol. Physiol. 1978; 5: 67-73

      219. Vajda, F. J. E., Mihaly, G. W., Miles, J. L., et al.: Rectal administration of sodium valproate in status epilepticus. Neurology, 28:897–899.

        • Vajda F.J.E.
        • Prineas R.J.
        • Lovell R.R.H.
        Interaction between phenytoin and the benzodiazepine.
        Br. Med. J. 1971; 1: 346
        • Vajda F.
        • Williams F.M.
        • Davidson S.
        • et al.
        Human brain, cerebrospinal fluid, and plasma concentrations of diphenylhydantoin and phenobarbital.
        Clin. Pharmacol. Ther. 1974; 15: 597-603
        • Vandemark F.L.
        • Adams R.F.
        Ultramicro gas-chromatographic analysis for anticonvulsants, with use of a nitrogen-selective detector.
        Clin. Chem. 1976; 22: 1062-1065
        • Villarreal H.J.
        • Wilder B.J.
        • Bauman A.W.
        • et al.
        Effect of valproic acid on spike and wave discharges in patients with absence seizures.
        Neurology. 1978; 28: 886-891
        • Wallace J.E.
        • Hamilton H.E.
        • Schimek Jr., E.L.
        • et al.
        Determination of primidone by electron-capture gas chromatography.
        Anal. Chem. 1977; 49: 903-906
        • Wallace J.E.
        • Schweriner H.A.
        • Hamilton H.E.
        • et al.
        Electrocapture gas-liquid chromatographic determination of ethosuximide and desmethylmethsuximide in plasma or serum.
        Clin. Chem. 1979; 25: 252-255
        • Wallis W.
        • Kutt H.
        • McDowell F.
        Intravenous diphenylhydantoin in treatment of acute repetitive seizures.
        Neurology (Minneap.). 1968; 18: 513-525
        • Werner M.
        • Mohrbacher J.
        • Riendeau C.J.
        Gas-liquid chromatography of underivatized drugs after chromatographic extraction from blood.
        Clin. Chem. 1979; 25: 2020-2025
        • Westenberg H.G.M.
        • van der Kleijn E.
        • Oei T.T.
        • et al.
        Kinetics of carbamazepine and carbamazepine-epoxide, determined by use of plasma and saliva.
        Clin. Pharmacol. Ther. 1978; 23: 320-328
        • Weinstein A.W.
        • Allen R.J.
        Ethosuximide treatment of petit mal seizures.
        Am. J. Dis. Child. 1966; 111: 63-73
        • Wilder B.J.
        • Willmore L.J.
        • Bruni J.
        • et al.
        Valproic acid: Interaction with other anticonvulsant drugs.
        Neurology. 1978; 28: 892-896
        • Wilensky A.J.
        • Lowden J.A.
        Inadequate serum levels after intramuscular administration of diphenylhydantoin.
        Neurology (Minneap.). 1973; 23: 318-324
        • Williams R.T.
        Progress report: Hepatic metabolism of drugs.
        Gut. 1972; 13: 579-585
        • Woodbury D.M.
        Role of pharmacological factors in the evaluation of anticonvulsant drugs.
        Epilepsia. 1969; 10: 121-124
        • Zimmerman F.T.
        • Burgemeister B.B.
        A new drug for petit mal epilepsy.
        Neurology (Minneap.). 1958; 8: 769-775

      Article info

      Identification

      DOI: https://doi.org/10.1016/S0272-2712(18)31086-2

      Copyright

      © 1981 Elsevier Inc. Published by Elsevier Inc. All rights reserved.

      ScienceDirect

      Access this article on ScienceDirect
      We use cookies to help provide and enhance our service and tailor content. To update your cookie settings, please visit the for this site.
      Copyright © 2023 Elsevier Inc. except certain content provided by third parties. The content on this site is intended for healthcare professionals.


      RELX