Kinetics of a naltrexone sustained-release preparation

Abstract

A biodegradable sustained-release naltrexone bead preparation containing 70% naltrexone in a physical mixture with a copolymer of 90% lactic acid and 10% glycolic acid was evaluated in three male subjects. Each subject received a 10-mg iv dose of naltrexone HCl and a 63-mg dose by subcutaneous implantation of naltrexone beads. Kinetics of naltrexone estimated from the intravenous dose indicated a plasma clearance range of 3.1 to 3.4 l/min and a t 1/2 range of 1.7 to 3.7 hr. After bead implantation, average plasma naltrexone levels were maintained at 0.3 to 0.4 ng/ml and naltrexol levels were at 0.4 to 1.0 ng/ml for a period of approximately 1 mo, during which urine naltrexone and naltrexol levels were about 20 to 30 and 70 to 200 ng/ml. It was estimated that approximately 70% to 77% of the dose was absorbed after bead implantation. There were no serious adverse effects other than tissue irritation in two of the three subjects.