Introduction:We investigated the pharmacokinetic characteristics of milrinone in critically ill children, a group in which pharmacokinetic data are limited. Methods:Fourteen children were enrolled and received a loading dose followed by a continuous infusion. Four to 9 timed blood samples were collected from each patient: prior to milrinone, at the end of the loading dose (C1), ≈24 hours later (C2), prior to (C3), and after stopping the infusion. [Milrinone] of extracted serum samples was measured by HPLC. The milrinone half-life (t1/2), steady state clearance (CLss), and volume of distribution (Vd) were calculated assuming 1st-order elimination with an open 1-compartment model. Results: The loading dose of milrinone (48.5±1.9 mcg/kg) resulted in C1 of 185 ±60 ng/ml and continuous infusion (0.5 mcg/kg/min) was associated with C2 of 83.4 ± 29.1 ng/ml. At discontinuation of the drug (in 5.3 ± 2.7 days) C3 was 61.4 ± 18 ng/ml (C2 v C3, p=ns). CLss was 8.2 ± 2.7 ml/kg/min, Vd was 0.66± 0.38 L/kg, and t1/2 was 58 ± 38 minutes. One patient developed multi-organ system failure (MOSF) and received an infusion of 0.25 mcg/kg/min: C3 was 241 ng/ml, [milrinone] was >200 ng/ml 2 hours after stopping the infusion, CLss was 1.0 ml/kg/min and t1/2 was markedly prolonged (> 8 hours). Excluding the patient with MOSF, age was not correlated with any kinetic parameter. However, C2 increased with increasing serum creatinine and bilirubin (p<0.05) and Vd increased with increasing bilirubin (p<0.05). Conclusions:Milrinone pharmacokinetics in this group of critically ill children are similar to those in a small group of pediatric cardiac surgery patients[1]. A loading dose of 50 mcg/kg followed by continuous infusion of 0.5 mcg/kg/min yielded drug concentrations initially in the range associated with effective therapy in adults(>100 ng/ml)[2]. However, [milrinone] declined during the infusion, suggesting a need to study increased infusion rates in children. Milrinone should be used with great care or avoided entirely in children with MOSF.
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Baird, J., Ushay, H. & Notterman, D. Milrinone Pharmacokinetics in Critically Ill Children 179. Pediatr Res 43 (Suppl 4), 33 (1998). https://doi.org/10.1203/00006450-199804001-00200
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DOI: https://doi.org/10.1203/00006450-199804001-00200