J Clin Pharmacol
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DRUG INTERACTIONS

The Effects of Ergoloid Mesylates and Ginkgo Biloba on the Pharmacokinetics of Ticlopidine

Wen-Jen Lu, PhD, Jin-ding Huang, PhD and Ming-Liang Lai, MD

From the Institute of Basic Medical Sciences and Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (Dr Lu, Dr Huang); and the Department of Neurology, College of Medicine, National Cheng Kung University, Tainan, Taiwan (Dr Lai).

Ticlopidine is sometimes coadministered with ergoloid mesylates or ginkgo biloba in clinical situations. Our objective was to examine the effect of ergoloid mesylates and ginkgo biloba on ticlopidine pharmacokinetics. Ticlopidine, ergoloid mesylates, and ginkgo biloba significantly inhibited the organic anion transporting polypeptide (OATP-B)-mediated uptake of [3H]-estrone-3-sulfate in a concentration-dependent manner. When ergoloid mesylates was coadministered with ticlopidine, the ticlopidine area under the plasma drug concentration-time profile (AUC) from 0 to 12 hours was decreased 30% and the peak plasma drug concentration (Cmax) was decreased 29%, compared with ticlopidine administration alone. There were no significant changes in the pharmacokinetic parameters of ticlopidine when it was coadministered with ginkgo biloba. In summary, ergoloid mesylates is a more potent inhibitor of OATP-B than is ginkgo biloba, and it can reduce the oral bioavailability of drugs transported by OATP-B. Ergoloid mesylates markedly decreased the AUC and Cmax of ticlopidine, probably by inhibiting the OATP-B-mediated uptake of ticlopidine during the intestinal absorption phase. The results support a new model of intestinal drug-drug interaction.

Key Words: Ergoloid mesylates • ginkgo biloba • ticlopidine

Address for reprints: Ming-Liang Lai, MD, Department of Neurology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; e-mail: amatalai{at}mail.ncku.edu.tw.


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