In vivo release and absorption of naltrexone implants in different species of animals

OBJECTIVE To investigate the effects of the differences of animal species and implant locations on absorption in vivo and the correlation of the release in vitro and the absorption in vivo.METHODS Naltrexone implants (NTXIMPs) were implanted subcutaneously in mice,rats,rabbits and dogs,respectively,and also implanted intramuscularly in rabbits.The in vivo liberation of NTX from implants was detected by measuring the residual NTX amount in the implants using spectrophotometrical method.The absorption of NTX was monitored through measurement of the NTX concentrations in plasma,liver and kidney using HPLC.RESULTS Although the differences of animal species and implant locations affected the in vivo release profiles of NTXIMPs,the correlation between in vivo and in vivo release of NTX from implants were excellent (P0.01).The difference of in vivo release of NTX from implants was dependent on the adipose tissue distribution.The effects of the different animal species was a little more remarkable than that of different implant locations on in vivo release of NTX from implants.A fairly constant NTX plasma level was observed during the implantation in all the animal species studied,indicating that NTXIMPs could maintain fourweek therapeutic effects after subcutaneous implantation.The constant NTX concentrations and total amounts in the liver and kidney of mice and rats also indicated that there was no drug accumulation during implantation.CONCLUSION In vivo release profiles of NTXIMPs were affected by both the different animals species and different implant locations.Good correlation of in vitro and in vivo release was observed in NTXIMPs.Single implantation of NTXIMPs may maintain the therapeutical effect more than 4 weeks.