PHARMACOKINETICS OF RHEOTHRX INJECTION IN HEALTHY MALE-VOLUNTEERS

The objectives of this study were to evaluate the safety and tolerabil ity of RheothRx (poloxamer 188) Injection administered as an intraveno us (iv) infusion to healthy male volunteers and to determine the pharm acokinetic profile of poloxamer 188. Thirty-six healthy male volunteer s were enrolled in a randomized, double-blind, placebo-controlled, dos e-escalation trial for RheothRx Injection. The volunteers were randomi zed to three treatment groups (12 per treatment group, with eight rece iving active therapy and four receiving placebo). In each treatment gr oup, volunteers received RheothRx Injection or placebo as an iv infusi on on two occasions at least 3 weeks apart to make a total of six dose s being studied (10, 30, and 45 mg/kg/h for 72 h, 60 mg/kg/h for 43.3 to 72 h, 60 and 90 mg/kg/h for 24 h). Serial plasma samples were colle cted during and up to 36 h after the end of the infusions; urine was c ollected over intervals from the start of the infusion until 36 h afte r the infusions were terminated. Plasma and urine samples were assayed for poloxamer 188 by gel-permeation chromatography. Pharmacokinetic p arameter values were calculated by noncompartmental and compartmental methods. Poloxamer 188 was eliminated primarily by renal excretion. Es timates of clearance, elimination rate constant, and apparent volume o f distribution at steady state values were independent of infusion rat e, Poloxamer 188 displayed no apparent infusion rate dependence in its pharmacokinetics.