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Pharmacokinetics and pharmacodynamics of sibrafiban alone or in combination with ticlopidine and aspirin
Author(s) -
Wittke, Bärbel,
Ensor, Hilary,
Chung, Jain,
Birnböck, Herbert,
Lausecker, Berthold,
Ertel, Sylvie I.,
Mackie Ian J.,
Machin Samuel J.
Publication year - 2000
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2000.049003231.x
Subject(s) - ticlopidine , aspirin , pharmacodynamics , pharmacology , pharmacokinetics , medicine , platelet aggregation inhibitor , chemistry , clopidogrel
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 therapyMethods 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.