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Ticlopidine inhibits phenytoin clearance
S Donahue1, D A Flockhart, D R Abernethy
1Division of Clinical Pharmacology, Georgetown University School of Medicine, Washington, DC, USA.
Clinical Pharmacology and Therapeutics
|December 29, 1999
Summary
Ticlopidine significantly increases phenytoin
Area of Science:
- Pharmacology
- Drug Metabolism
- Clinical Pharmacy
Background:
- Phenytoin toxicity cases reported with ticlopidine.
- Need to understand drug interaction mechanisms.
Purpose of the Study:
- Investigate ticlopidine's effect on phenytoin pharmacokinetics.
- Determine if ticlopidine alters phenytoin metabolism.
Main Methods:
- Six patients on phenytoin monotherapy studied.
- Phenytoin pharmacokinetics measured with and without ticlopidine.
- Michaelis-Menten kinetics (Km, Vmax) calculated.
Main Results:
- Mean phenytoin Km significantly increased with ticlopidine (5.8 to 12.3, P=.02).
- Ticlopidine did not significantly alter phenytoin Vmax.
- Ticlopidine inhibited phenytoin clearance.
Conclusions:
- Ticlopidine alters phenytoin pharmacokinetics.
- Dosage adjustment of phenytoin is recommended with ticlopidine.
- Ticlopidine inhibits CYP2C19, impacting phenytoin metabolism.