Clinical evaluation of a naltrexone sustained-release preparation

Abstract

A clinical evaluation of the naltrexone bead, a biodegradable sustained-release dosage form of 3.0 mg in weight containing 70% naltrexone in a copolymer of lactic and glycolic acids, was carried out in 4 healthy normal males. Subjects were given an intravenous dose of 10 mg naltrexone and approx. 1 week later a 63-mg dose of naltrexone by subcutaneous administration of the beads. Challenge doses of 15 mg morphine were given to each subject during the study for the assessment of narcotic blockade effects of naltrexone. For a 2–4-week period after bead administration, relatively constant plasma levels were maintained at 0.30–0.46 ng/ml for naltrexone and were 0.64–1.07 ng/ml for naltrexol. Urine levels for unchanged and conjugated naltrexone were 79–215 ng/ml and for naltrexol were 315–500 ng/ml. From kinetic analysis, an average of 2.4–2.7% of implanted dose was absorbed each day from the administration of the beads. Opiate effects of morphine challenges were mitigated during the 2–4-week period after administration of naltrexone beads.