Reuning R H, Liao S H, Staubus A E, Ashcraft S B, Downs D A, Harrigan S E, Wiley J N, Wise D L
J Pharmacokinet Biopharm. 1983 Aug;11(4):369-87. doi: 10.1007/BF01058956.
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.
在猴子身上，已对控释给药系统中纳曲酮的释放速率进行了超过一个月时间的定量研究。该方法需要利用静脉推注剂量校准每只猴子的药代动力学参数，并测定给药后血浆中未变化的纳曲酮水平随时间的变化情况。还需要在给药系统给药后定期获取血浆中未变化的纳曲酮水平。然后计算释放速率以及释放的总量。将该方法应用于三只猴子体内的可生物降解共聚物纳曲酮给药系统，结果显示在最初的3 - 5天内，每天的初始释放速率为剂量的3 - 8%，随后从第5天到最后一个可测量血浆样本的时间（36 - 43天），释放速率缓慢且相当恒定，为每天1 - 3%。使用实验和模拟的血浆纳曲酮数据对替代计算方法进行比较，验证了释放速率计算的准确性。在两只获得完整数据的猴子中，计算得出的纳曲酮释放总量加上从动物体内取出后给药系统中检测到的剩余量，占给药剂量的91 - 94%。
