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An interaction between cytostatic and anticonvulsant drugs
Author(s) -
Neef Cees,
Voogdvan der Straaten Ingrid
Publication year - 1988
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1988.45
Subject(s) - carbamazepine , phenytoin , volume of distribution , anticonvulsant , cisplatin , pharmacology , drug interaction , clinical pharmacology , drug , distribution (mathematics) , pharmacokinetics , medicine , chemotherapy , chemistry , epilepsy , mathematical analysis , mathematics , psychiatry
A young woman with epilepsy had tonic‐clonic seizures during antineoplastic therapy with adriamycin and cisplatin. During two courses of cytostatic drug administration peak and trough plasma levels of phenytoin, carbamazepine, and valproate sodium were measured. Lower plasma levels of carbamazepine and valproate sodium were observed after 2 days of antineoplastic therapy. Normal plasma levels of these drugs were found 2 to 3 days after the last cisplatin dose. Impaired absorption or accelerated elimination might explain these results. Phenytoin levels were reduced to 37% of the original values, although the drug was given intravenously. Changed Michaelis‐Menten parameters suggest that cisplatin increases the metabolic rate of phenytoin. Another explanation for the decreased drug levels might be an increased volume of distribution. Calculation of this volume from peak and trough levels showed an increase of the volume of distribution during and after chemotherapy. Clinical Pharmacology and Therapeutics (1988) 43, 372–375; doi: 10.1038/clpt.1988.45