Population Pharmacokinetics of Milrinone in Neonates with Hypoplastic Left Heart Syndrome Undergoing Stage I Reconstruction

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Abstract
We performed a blinded, randomized pharmacoki- netic study of milrinone in 16 neonates with hypo- plastic left heart undergoing stage I reconstruction to determine the impact of cardiopulmonary bypass and modified ultrafiltration on drug disposition and to define the drug exposure during a continuous IV infusion of drug postoperatively. Neonates received an initial dose of either a 100 or 250 g/kg of milri- none into the cardiopulmonary bypass circuit at the start of rewarming. Postoperatively, milrinone was infused to clinical needs. A mixed-effect modeling approach was used to characterize milrinone phar- macokinetics during cardiopulmonary bypass, mod- ified ultrafiltration, and postoperatively using the NONMEM algorithm. All patients in this study demon- strated a modified ultrafiltration concentrating effect that