Novel depots of buprenorphine prodrugs have a long-acting antinociceptive effect.
An analgesic with a prolonged duration may be desirable in patients with long-lasting pain. In this study, we evaluated the antinociceptive effects and durations of action of three novel depots of buprenorphine esters buprenorphine propionate, enanthate, and decanoate given by IM injection, in rats. The pharmacokinetic profiles of buprenorphine in blood after IM injection of these depots were also evaluated. Antinociception was evaluated using the plantar test. Buprenorphine concentrations in blood were assayed using high-performance liquid chromatography. We found that the traditional form of buprenorphine HCl (in saline) produced a dose-related antinociceptive effect. A dose of 0.6 micromol/kg buprenorphine HCl (in saline) produced a significant antinociceptive effect lasting 5 h. The same dose of buprenorphine base, propionate, enanthate, and decanoate (in oil) also produced a significant antinociceptive effect with longer durations of action of 26, 28, 52, and 70 h, respectively. The pharmacokinetic studies demonstrated that all the buprenorphine esters were prodrugs of buprenorphine. We conclude that the novel depots of buprenorphine prodrugs: buprenorphine propionate, enanthate, and decanoate produced a long-acting antinociceptive effect after IM injection in rats.
Liu
Kuo-Sheng
KS
Department of Anesthesiology and Medical Research, Chi-Mei Medical Center, Tainan, Taiwan.
Tzeng
Jann-Inn
JI
Chen
Yu-Wen
YW
Huang
Kuo-Lun
KL
Kuei
Chun-Hsiung
CH
Wang
Jhi-Joung
JJ
D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D002047:Buprenorphine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D010147:Pain Measurement / Q000187:drug effects*; D011355:Prodrugs / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D011355:Prodrugs; D002047:Buprenorphine