Clopidogrel activities in patients with renal function impairment

Area of Science:

• Pharmacology
• Nephrology
• Cardiology

Background:

• Renal failure impacts drug pharmacokinetics and pharmacodynamics.
• Clopidogrel (Plavix) is an antiplatelet medication commonly used in cardiovascular disease.
• The safety and efficacy of clopidogrel in renal impairment require specific investigation.

Purpose of the Study:

• To evaluate the tolerability of repeated clopidogrel doses in patients with renal failure.
• To assess the pharmacodynamic effects, specifically platelet aggregation and bleeding time.
• To determine the pharmacokinetic parameters of clopidogrel and its metabolite in patients with moderate and severe renal impairment.

Main Methods:

• An open, uncontrolled, parallel-group study involving 16 patients (8 moderate, 8 severe renal failure).
• Daily administration of 75mg clopidogrel for 8 days.
• Measurements included ADP-induced platelet aggregation, skin bleeding time, plasma concentrations, and urinary excretion of clopidogrel and its metabolite (SR 26334).

Main Results:

• Clopidogrel demonstrated equal inhibition of platelet aggregation (~25%) and extension of bleeding time (x2) in both groups.
• No significant differences in Cmax and Tmax of clopidogrel were observed between groups.
• Urinary excretion and renal clearance of SR 26334 were lower in severe renal failure, but elimination half-lives were similar. Trough levels and AUC(0-24h) were higher in moderate impairment.

Conclusions:

• Clopidogrel 75mg once daily is well-tolerated in patients with moderate or severe renal failure.
• The drug provides effective inhibition of ADP-induced platelet aggregation without excessive bleeding.
• Dose adjustment of clopidogrel does not appear necessary for patients with moderate to severe renal failure.