Bioequivalence of ticlopidine hydrochloride administered in single dose to healthy volunteers.
Ticlopidine hydrochloride (CAS 55142-85-3) is an inhibitor of platelet aggregation used in the management and prevention of thromboembolic disorders.A new formulation of ticlopidine hydrochloride (test) was compared to the reference Tiklid, present in the market, in order to assess their bioequivalence and to register the new formulation as a generic according to the Abbreviated New Drug Application (ANDA) procedure.Twenty-four healthy male volunteers were treated with the two formulations (one tablet containing 250mg of active ingredient) according to a single-dose, balanced, crossover, double-blind design with a washout between the two study periods. Plasma concentration of ticlopidine was assayed in timed samples over a 24h-period with a well-validated HPLC method with UV detection, which allowed 5ngml(-1) to be assayed as the lowest quantifiable concentration. The double-blind key was disclosed only after having completed the assay of unknown samples. From plasma concentrations, C(max), t(max), AUC(0-t), AUC(0- infinity ) and t(1/2) were evaluated through non-compartmental pharmacokinetic analysis. C(max) and AUCs were log(10)- transformed and statistically processed using crossover ANOVA. No statistically significant formulation, period, or sequence effect was encountered. Ninety percent confidence intervals of C(max) and AUCs were comprised in the stipulated 0.80-1.25 range. Similarly, Schuirmann's test led to statistically significant degrees on both the sides explored. Time to peak, t(max), processed with the non-parametric Kruskal-Wallis' test, did not show any statistically significant degree. According to guidelines operating in Europe, the test formulation of ticlopidine hydrochloride can be declared bioequivalent with the reference, both formulations in 250mg tablets.
Marzo
Antonio
A
IPAS SA, Via Mastri 36, 6853 Ligornetto, Switzerland.
Dal Bo
Lorenzo
L
Rusca
Antonio
A
Zini
Pierangelo
P
D000328:Adult; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D013988:Ticlopidine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D010975:Platelet Aggregation Inhibitors; D013988:Ticlopidine