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Amrinone-associated thrombocytopenia: pharmacokinetic analysis
M P Ross1, E M Allen-Webb, J B Pappas
1University of Utah Medical Center, Department of Pediatrics, Salt Lake City.
Clinical Pharmacology and Therapeutics
|June 1, 1993
Summary
N-acetylamrinone, not amrinone, may cause thrombocytopenia in children post-heart surgery. Higher levels of N-acetylamrinone correlated with lower platelet counts, suggesting it as the toxic agent.
Area of Science:
- Pharmacology
- Pediatric Cardiology
- Hematology
Background:
- Amrinone-associated thrombocytopenia is a known complication.
- The exact mechanism, whether amrinone or its metabolite N-acetylamrinone, remains unclear.
- Platelet destruction is hypothesized to be a concentration-dependent toxic effect.
Purpose of the Study:
- To investigate the relationship between amrinone and N-acetylamrinone pharmacokinetics and thrombocytopenia in children.
- To determine if amrinone or N-acetylamrinone is the primary mediator of amrinone-induced thrombocytopenia.
Main Methods:
- Prospective evaluation of 18 children receiving amrinone post-heart surgery.
- Pharmacokinetic analysis of amrinone and N-acetylamrinone plasma concentrations using HPLC.
- Concurrent monitoring of platelet counts throughout amrinone therapy.
Main Results:
- Eight out of 18 patients developed thrombocytopenia (platelet count 66 +/- 17 x 10(9)/L).
- No significant differences in amrinone concentrations or exposure were observed between patients with and without thrombocytopenia.
- Patients with thrombocytopenia had higher peak and steady-state concentrations of N-acetylamrinone, as well as a greater N-acetylamrinone area under the curve (AUC).
Conclusions:
- N-acetylamrinone, rather than amrinone itself, is likely responsible for amrinone-associated thrombocytopenia in pediatric patients.
- These findings suggest a shift in focus towards N-acetylamrinone levels for managing and preventing thrombocytopenia in children treated with amrinone.