AMRINONE-ASSOCIATED THROMBOCYTOPENIA - PHARMACOKINETIC ANALYSIS

Amrinone-associated thrombocytopenia is thought to result from nonimmu ne-mediated peripheral platelet destruction. Platelet destruction may be a concentration-dependent toxic effect of amrinone or its principal metabolite N-acetylamrinone. Eighteen children receiving amrinone aft er heart surgery were prospectively evaluated to correlate the pharmac okinetics of amrinone and N-acetylamrinone with thrombocytopenia. Amri none and N-acetylamrinone plasma concentrations were determined by HPL C during loading, infusion, and terminal elimination, with concurrent monitoring of platelet counts. Thrombocytopenia developed in eight pat ients (platelet count, 66 +/- 17 x 10(9) platelets/L [mean +/-SD]). Pe ak and steady-state amrinone plasma concentration, amrinone total dose , duration of amrinone exposure, and amrinone area under curve (AUC) w ere similar between patients with and without thrombocytopenia. N-Acet ylamrinone peak concentration, steady-state concentration, N-acetylamr inone AUC, and ratio of N-acetylamrinone to amrinone were greater in p atients with thrombocytopenia. This association suggests that N-acetyl amrinone, and not amrinone, may be the mediator of thrombocytopenia in children receiving amrinone.