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Studies With Stable Isotopes I: Changes in Phenytoin Pharmacokinetics and Biotransformation During Monotherapy
Author(s) -
Browne Thomas R.,
Evans James E.,
Szabo George K.,
Evans Barbara A.,
Greenblatt David J.,
Schumacher Gerald E.
Publication year - 1985
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1985.tb02799.x
Subject(s) - pharmacokinetics , phenytoin , chemistry , excretion , biotransformation , anticonvulsant , pharmacology , half life , elimination rate constant , medicine , endocrinology , volume of distribution , epilepsy , biochemistry , psychiatry , enzyme
Six patients were given tracer doses of 13 C 15 N 2 ‐phenytoin (PHT) before and four and 12 weeks after beginning monotherapy. The following significant ( P < .05) changes occurred during monotherapy: (1) Apparent (from tracer doses) PHT total clearance by linear method decreased; (2) apparent PHT elimination half‐life increased; (3) apparent mean PHT serum concentration per unit dose increased; (4) apparent rate of excretion of p‐hydroxyphenyl‐phenylhydantoin (p‐HPPH) decreased; (5) apparent rate of excretion of PHT dihydrodiol increased; and (6) apparent PHT total clearance and elimination half‐life and apparent p‐HPPH rate of excretion were dose dependent. Phenytoin apparent pharmacokinetic and biotransformation values undergo a typical series of changes after beginning monotherapy at typical dosing rates, because PHT's dose‐dependent pharmacokinetics result in differing apparent vaiues as the serum concentration rises to steady state. Stable iostope methods are particularly suitable for investigating such phenomena .