In vitro and in vivo pharmacokinetics of two novel 1,3-cyclic propanyl phosphate ester prodrugs of 18β-glycyrrhetic acid in rats

Abstract

The in vitro metabolism of two novel phosphate prodrugs of glycyrrhetic acid (GA) was studied by the method of incubation in the rat liver microsome and the in vivo plasma pharmacokinetics after injecting intravenously (i.v.) into six rats was investigated, respectively. The prodrugs diminished gradually with time and most of the parent drugs were released in 30 min in vitro. In this paper, the in vivo plasma concentration data were analyzed by compartmental modeling. Both the prodrugs and the corresponding released parent drugs could be described by a two-compartment model, which existed for 48 h in rats. The t _1/2 increases remarkably after i.v. administration to rats when compared with injecting the parent drugs directly.

Keywords:

• pharmacokinetics
• cyclic propanyl phosphate ester
• prodrug
• liver microsome
• mechanism of the metabolism
• compartment model

Acknowledgements

We are grateful to Mr Wei-Zhi Sun (Key Laboratory of Marine Drugs, Ministry of Education, Marine Drug and Food Institute, Ocean University of China) for the preparation of samples. We also gratefully acknowledge Ms Xiu-Li Zhang and Su-Mei Ren (Key Laboratory of Marine Drugs, Ministry of Education, Marine Drug and Food Institute, Ocean University of China) for the measurement of ESI-TOF-MS and NMR spectra, respectively.