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Titolo:
Ticlopidine inhibits phenytoin clearance
Autore:
Donahue, S; Flockhart, DA; Abernethy, DR;
Indirizzi:
Georgetown Univ, Sch Med, Div Clin Pharmacol, Washington, DC USA Georgetown Univ Washington DC USA Div Clin Pharmacol, Washington, DC USA
Titolo Testata:
CLINICAL PHARMACOLOGY & THERAPEUTICS
fascicolo: 6, volume: 66, anno: 1999,
pagine: 563 - 568
SICI:
0009-9236(199912)66:6<563:TIPC>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
CLINICAL PHARMACOKINETICS; METABOLISM; P4502C19;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
18
Recensione:
Indirizzi per estratti:
Indirizzo: Abernethy, DR NIA, Clin Invest Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA NIA 5600 Nathan Shock Dr Baltimore MD USA 21224 MD 21224 USA
Citazione:
S. Donahue et al., "Ticlopidine inhibits phenytoin clearance", CLIN PHARM, 66(6), 1999, pp. 563-568

Abstract

Because cases of phenytoin toxicity during concomitant ticlopidine therapyhave been reported, we investigated the effects of multiple doses of ticlopidine on phenytoin pharmacokinetics in six patients receiving phenytoin monotherapy, Two steady-state dosing rate and serum phenytoin minimum concentration (C-min) pairs were obtained for each patient administered oral phenytoin alone, then phenytoin plus 250 mg ticlopidine twice daily. All patients had serum C-min ticlopidine values of 0.06 to 0.25 mu g/mL when receivingticlopidine, Individual pharmacokinetic parameters for phenytoin were calculated. The Michaelis-Menten constant (K-m) was determined as the slope andmaximum velocity (V-max; equivalent to the maximal rate of elimination or the maximum daily dose that can be metabolized) as the y-intercept of the Linear Michaelis-Menten plot. Mean phenytoin K-m significantly increased from 5.8 to 12.3 during ticlopidine coadministration compared with administration of phenytoin alone (P = .02), Mean phenytoin V-max was not significantly changed by the coadministration of ticlopidine. These data indicate that ticlopidine inhibits the clearance and alters the clinical pharmacokineticsof phenytoin so that dosage adjustment of phenytoin should be considered when ticlopidine is coadministered, The results are consistent with previoushuman liver microsome findings that ticlopidine is a potent inhibitor of CYP2C19, a P450 isozyme that is significantly responsible for phenytoin metabolism.

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Documento generato il 28/01/20 alle ore 02:24:54