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.
University of Utah Medical Center, Department of Pediatrics, Salt Lake City.
M P
MP
Ross
E M
EM
Allen-Webb
J B
JB
Pappas
E C
EC
McGough
D000676:Amrinone / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D008657:Metabolic Clearance Rate; D010976:Platelet Count; D012307:Risk Factors; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced*
C023499:N-acetylamrinone; D000676:Amrinone