Article date: March 2000
By: Bärbel Wittke,, Hilary Ensor,, Jain Chung,, Herbert Birnböck,, Berthold Lausecker,, Sylvie I. Ertel,, Ian J. Mackie, Samuel J. Machin, in Volume 49, Issue 3, pages 231-239
Aims The purpose of this clinical study was to evaluate the effects of a ticlopidine/aspirin combination on the pharmacokinetics and pharmacodynamics of sibrafiban and the tolerability of the combination therapy
Methods Thirty‐eight healthy male volunteers were randomized to receive one of the following treatments for 7 days: sibrafiban (n = 12), ticlopidine/aspirin (n = 12), or the combination treatment sibrafiban/ticlopidine/aspirin (n = 14). Concentrations of the active metabolite of sibrafiban, Ro 44–3888, in plasma and urine were determined by column‐switching liquid chromatography combined with tandem mass spectrometry. The pharmacodynamics of sibrafiban and ticlopidine/aspirin were examined by measuring the inhibition of ADP‐ or collagen‐induced platelet aggregation.
Results The addition of ticlopidine/aspirin to sibrafiban did not significantly alter the pharmacokinetic parameters of Ro 44–3888. the geometric mean ratio for AUC(0,12h) was 110 (95% CI 0.82, 1.22). Separately, sibrafiban and ticlopidine/aspirin inhibited ADP‐and collagen‐induced platelet aggregation and the effects of the two treatments were additive. For example, the average inhibition of ADP‐induced platelet aggregation over 12 h was 42% in the sibrafiban treated group, 55% in the ticlopidine/aspirin group and 69% in the sibrafiban/ticlopidine group. The bleeding time was prolonged in the treatments with ticlopidine/aspirin (8.1 min) and sibrafiban/ticlopidine/aspirin (8.6 min) compared with sibrafiban alone (3.5 min).
Conclusions This study shows a significant pharmacodynamic interaction between sibrafiban and ticlopidine/aspirin. Consequently, the simultaneous administration of sibrafiban and ticlopidine/aspirin should be carefully monitored to ensure the patient’s coverage with an antiplatelet drug without exposure to an excessive bleeding risk.
DOI: 10.1046/j.1365-2125.2000.049003231.x
View this article