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Amrinone‐associated thrombocytopenia: Pharmacokinetic analysis
Author(s) -
Ross Mitchell P,
AllenWebb Elizabeth M,
Pappas Jannette B,
McGough Edwin C
Publication year - 1993
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1993.87
Subject(s) - amrinone , pharmacokinetics , platelet , metabolite , medicine , active metabolite , pharmacology , chemistry , inotrope
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