Amrinone‐associated thrombocytopenia: Pharmacokinetic analysis

Amrinone‐associated thrombocytopenia is thought to result from nonimmune‐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 after heart surgery were prospectively evaluated to correlate the pharmacokinetics of amrinone and N ‐acetylamrinone with thrombocytopenia. Amrinone and N ‐acetylamrinone plasma concentrations were determined by HPLC during loading, infusion, and terminal elimination, with concurrent monitoring of platelet counts. Thrombocytopenia developed in eight patients (platelet count, 66 ± 17 x 10 9 platelets/L [mean ± SD]). Peak and steady‐state amrinone plasma concentration, amrinone total dose, duration of amrinone exposure, and amrinone area under curve (AUC) were similar between patients with and without thrombocytopenia. N ‐Acetylamrinone peak concentration, steady‐state concentration, N ‐acetylamrinone AUC, and ratio of N ‐acetylamrinone to amrinone were greater in patients with thrombocytopenia. This association suggests that N ‐acetylamrinone, and not amrinone, may be the mediator of thrombocytopenia in children receiving amrinone. Clinical Pharmacology and Therapeutics (1993) 53 , 661–667; doi: 10.1038/clpt.1993.87