Pharmacokinetics of Ticlopidine in the Rabbit

Abstract

Abstract There is no information about the pharmacokinetics of ticlopidine in rabbits. Such information is valuable in designing appropriate dosing regimens for experimental studies of the drug with ultimate applications in man. The disposition kinetics of ticlopidine at three dose levels were evaluated in three groups of six rabbits which received 10, 50 or 100 mg kg−1 drug once daily via the oral-gastric route. Blood samples were collected at predetermined times after the third dose. Plasma concentrations of the unchanged drug were determined by a validated liquid chromatography-mass spectrometry method with a limit of detection of 5 μg L−1. There was a disproportionate increase in the mean maximum plasma concentration (Cmax) and the area under the plasma drug-concentration-time curve (AUC) for the 10 and 50 mg kg−1 doses. The apparent terminal half-life (t 1/2β), apparent volume of distribution (Vdβ/F), and total plasma clearance (CLp/F) of the drug were all dose-dependent. For example, t1/2β for the 10, 50 and 100 mg kg−1 doses were 1.04 ± 0.10, 4.24 ± 1.92 and 12.80 ± 6.35 h, respectively, whereas the Vdβ/F values for the corresponding doses were 214 ± 31, 475 ± 221 and 998 ± 420 L kg−1, respectively. These results show that the 100-mg kg−1 dose produces plasma ticlopidine concentrations similar to those found in man after administration of 250 mg of the drug. It is suggested that 100 mg kg−1 might be the appropriate dose of ticlopidine for use in rabbit experimental studies with ultimate application to man.