Ticlopidine inhibits phenytoin clearance.
Article Details
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Donahue S, Flockhart DA, Abernethy DR
Ticlopidine inhibits phenytoin clearance.
Clin Pharmacol Ther. 1999 Dec;66(6):563-8. doi: 10.1053/cp.1999.v66.103277001.
- PubMed ID
- 10613611 [ View in PubMed]
- Abstract
Because cases of phenytoin toxicity during concomitant ticlopidine therapy have 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 (Cmin) pairs were obtained for each patient administered oral phenytoin alone, then phenytoin plus 250 mg ticlopidine twice daily. All patients had serum Cmin ticlopidine values of 0.06 to 0.25 microg/mL when receiving ticlopidine. Individual pharmacokinetic parameters for phenytoin were calculated. The Michaelis-Menten constant (Km) was determined as the slope and maximum velocity (Vmax; 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 Km significantly increased from 5.8 to 12.3 during ticlopidine coadministration compared with administration of phenytoin alone (P = .02). Mean phenytoin Vmax was not significantly changed by the coadministration of ticlopidine. These data indicate that ticlopidine inhibits the clearance and alters the clinical pharmacokinetics of phenytoin so that dosage adjustment of phenytoin should be considered when ticlopidine is coadministered. The results are consistent with previous human liver microsome findings that ticlopidine is a potent inhibitor of CYP2C19, a P450 isozyme that is significantly responsible for phenytoin metabolism.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Ticlopidine Cytochrome P450 2C19 Protein Humans UnknownSubstrateInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareFosphenytoinTiclopidine The serum concentration of Fosphenytoin can be decreased when it is combined with Ticlopidine. PhenytoinTiclopidine The serum concentration of Phenytoin can be decreased when it is combined with Ticlopidine.