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Titolo:
TICLOPIDINE INHIBITION OF PHENYTOIN METABOLISM MEDIATED BY POTENT INHIBITION OF CYP2C19
Autore:
DONAHUE SR; FLOCKHART DA; ABERNETHY DR; KO JW;
Indirizzi:
GEORGETOWN UNIV,MED CTR,DEPT MED,DIV CLIN PHARMACOL,ROOM NE403,MED DENT BLDG WASHINGTON DC 20007 GEORGETOWN UNIV,MED CTR,DEPT MED,DIV CLIN PHARMACOL WASHINGTON DC 20007 GEORGETOWN UNIV,MED CTR,DEPT PHARMACOL,DIV CLIN PHARMACOL WASHINGTON DC 20007
Titolo Testata:
Clinical pharmacology and therapeutics
fascicolo: 5, volume: 62, anno: 1997,
pagine: 572 - 577
SICI:
0009-9236(1997)62:5<572:TIOPMM>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
IN-VITRO; DRUG-INTERACTIONS; PHARMACOKINETICS; TOXICITY; HYDROXYLATION; MICROSOMES; P4502C19;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
29
Recensione:
Indirizzi per estratti:
Citazione:
S.R. Donahue et al., "TICLOPIDINE INHIBITION OF PHENYTOIN METABOLISM MEDIATED BY POTENT INHIBITION OF CYP2C19", Clinical pharmacology and therapeutics, 62(5), 1997, pp. 572-577

Abstract

A patient who had taken a stable dose of phenytoin for 2 years had a coronary stent placed for unstable angina and ticlopidine was added tohis therapeutic regimen. Twenty-five days later, he was hospitalized with acute symptomatic phenytoin toxicity and a serum concentration of46.5 mu g/ml. Determination of metabolic genotype revealed that the patient had a wild-type genotype for CTP2C9, CTP2C19, and CTP2D6. Usinghuman liver microsomes, we showed that ticlopidine is a potent inhibitor of cytochrome P450 2C19, with an estimated inhibition constant (K-i) of 3.7 +/- 0.2 mu mol/L. The influence of ticlopidine on CYP2C9, the other cytochrome P450 isoform that metabolizes phenytoin, is relatively weak, with a calculated K-i of 38.8 +/- 27 mu mol/L. These data suggest that, in this patient, phenytoin toxicity was caused by inhibition of CYP2C19 by ticlopidine, and the data emphasize the importance ofCYP2C19 in the metabolism of phenytoin.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/20 alle ore 07:22:22