Pharmacokinetics of ticlopidine in the rabbit

There is no information about the pharmacokinetics of ticlopidine in rabbit s. Such information is valuable in designing appropriate dosing regimens fo r experimental studies of the drug with ultimate applications in man. The d isposition kinetics of ticlopidine at three dose levels were evaluated in t hree 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 predeter mined times after the third dose. Plasma concentrations of the unchanged dr ug were determined by a validated liquid chromatography-mass spectrometry m ethod with a limit of detection of 5 mu g L-1. There was a disproportionate increase in the mean maximum plasma concentrat ion (C-max) and the area under the plasma drug-concentration-time curve (AU C) for the 10 and 50 mg kg(-1) doses. The apparent terminal half-life (t1/2 (beta)), apparent volume of distribution (Vd(beta)/F), and total plasma cle arance (CLP/F) of the drug were all dose-dependent. For example, t1/2(beta) for the 10, 50 and 100 mg kg(-1) doses were 1.04 +/- 0.10, 4.24 +/- 1.92 a nd 12.80 +/- 6.35 h, respectively, whereas the Vd(beta)/F values for the co rresponding doses were 214 +/- 31, 475 +/- 221 and 998 +/- 420 L kg(-1), re spectively. 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 d ose of ticlopidine for use in rabbit experimental studies with ultimate app lication to man.