Pharmacokinetics of RheothRx Injection in Healthy Male Volunteers

The objectives of this study were to evaluate the safety and tolerability of RheothRx (poloxamer 188) Injection administered as an intravenous (iv) infusion to healthy male volunteers and to determine the pharmacokinetic profile of poloxamer 188. Thirty-six healthy male volunteers were enrolled in a randomized, double-blind, placebo-controlled, dose-escalation trial for RheothRx Injection. The volunteers were randomized to three treatment groups (12 per treatment group, with eight receiving active therapy and four receiving placebo). In each treatment group, volunteers received RheothRx Injection or placebo as an iv infusion on two occasions at least 3weeks apart to make a total of six doses being studied (10, 30, and 45mg/kg/h for 72h, 60mg/kg/h for 43.3 to 72h, 60 and 90mg/kg/h for 24h). Serial plasma samples were collected during and up to 36h after the end of the infusions; urine was collected over intervals from the start of the infusion until 36h after the infusions were terminated. Plasma and urine samples were assayed for poloxamer 188 by gel-permeation chromatography. Pharmacokinetic parameter values were calculated by noncompartmental and compartmental methods. Poloxamer 188 was eliminated primarily by renal excretion. Estimates of clearance, elimination rate constant, and apparent volume of distribution at steady state values were independent of infusion rate. Poloxamer 188 displayed no apparent infusion rate dependence in its pharmacokinetics.