Biliary excretion and enterohepatic circulation of thienorphine and its glucuronide conjugate in rats
| Autor: | Jingting Deng, Xiaomei Zhuang, Guolin Shen, Hua Li, Zehui Gong |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | Acta Pharmaceutica Sinica B, Vol 2, Iss 2, Pp 174-180 (2012) |
| Druh dokumentu: | article |
| ISSN: | 2211-3835 2211-3843 |
| DOI: | 10.1016/j.apsb.2012.02.007 |
| Popis: | Thienorphine (TNP) is a new partial opioid agonist currently developed as a promising drug candidate with the intended clinical indication for the treatment of opioid dependence. The pharmacokinetic profile and biliary excretion of TNP and its glucuronide conjugate (TNP-Glu) were investigated after oral administration of TNP in rats. The concentrations of TNP and TNP-Glu were simultaneously quantified using a LC-MS/MS method. A double peak phenomenon was observed in TNP plasma concentration–time curves with the secondary peak appeared at 6–8 h. A slower decline of plasma concentrations in the terminal phase was observed for TNP with T1/2 of 7.01 h. TNP-Glu was the predominant component in rat plasma and bile. Its plasma level was about 10 times higher than TNP and the 24 h accumulative bile excretion rate was 23%. Enterohepatic circulation of TNP and TNP-Glu was evaluated using a paired rat model. In bile-donor rats, no double-peak was detected and the elimination half life of TNP was significantly shortened (3.71 h) when compared to intact rats (7.01 h, P |
| Databáze: | Directory of Open Access Journals |
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