Enoximone pharmacokinetics in infants

Abstract

Enoximone and enoximone sulphoxide concentrations were measured in plasma of 20 infants, median age 6.0 (range 0.6-49.7) weeks, during and after prolonged continuous infusions. Patients were given enoximone 1 mg kg-1 and an infusion at 10 μg kg-1 min -1 just before being weaned from cardiopulmonary bypass (CPB). The infusion was stopped when clinically indicated, after a median 97 (range 24-572) h. Arterial blood samples were taken 30 min and 12 h after CPB, every 24 h during the infusion, and then 2, 4, 8, 12 and 24 h after the infusion was stopped. Pharmacokinetic non-compartmental analysis was performed using TOPFIT software. Fourteen patients who retained normal hepatic function had a median (95% confidence intervals) clearance of 9.7 (6.3-14.1) ml min-1 kg -1, elimination half-life of 5.2 (2.4-6.8) h and a volume of distribution of 3.6 (2.0-5.7) litre kg-1. The six patients with significant hepatic dysfunction had a lower clearance, 5.7 (2.4-14.5) ml min-1 kg-1, and significantly longer elimination half-life, 7.6 (6.5-10.9) h (P=0.02). Enoximone sulphoxide half-life was significantly prolonged in three patients with renal dysfunction, 16.2 (10.5-17.7) h versus 6.9 (6.1-9.4) h (P=0.03). These results confirm that enoximone pharmacokinetics in infants is similar to that found in adults. The infusion rate of enoximone should be reduced if hepatic or renal dysfunction supervenes.