Pharmacokinetic quantitation of naltrexone controlled release from a copolymer delivery system.

Naltrexone release rates from a controlled release delivery system have been quantitated over a time period greater than one month in the monkey. The method requires calibration of the pharmacokinetic parameters of each monkey utilizing an intravenous bolus dose and assay of unchanged naltrexone levels in plasma as a function of time after dosing. Also required are periodic plasma levels of unchanged naltrexone obtained subsequent to administration of the delivery system. Release rates are then calculated as well as the total amount released. Application of the methodology to a biodegradable copolymer naltrexone delivery system in three monkeys showed an initial release rate of 3-8% of the dose per day over the first 3-5 days followed by a slow, rather constant release rate of 1-3% per day from day 5 to the time of the last measurable plasma sample (36-43 days). Comparison of alternative calculation methods using both experimental and simulated plasma naltrexone data verified the accuracy of the release rate calculations. The sum of the calculated total amount of naltrexone released plus the assayed amount remaining in the delivery system after removal from the animal accounted for 91-94% of the administered dose in the two monkeys in which complete data were obtained.