Enterohepatic Recirculation of Free and Conjugated Silybin Following Administration of a Chewing Gum with Milk Thistle Extract | |
I. Grabnar(1), M. Pišlar(1), L.Maggi(2), D. Hasa(3), D. Voinovich(3) | |
(1) Faculty of Pharmacy, University of Ljubljana, Slovenia; (2) Department of Pharmaceutical Sciences, University of Pavia, Italy; (3) Department of Chemical and Pharmaceutical Sciences, University of Trieste, Italy | |
Poster: Absorption and Physiology-Based PK | |
Objectives: Silybin is the main ingredient of silymarin, a milk thistle extract, with recognised anti-hepatotoxic and free radical scavenging activity. Due to low oral bioavailability, a new chewing gum device 3TabGum has been developed. Silybin is rapidly metabolised to sulphate and glucuronide conjugates. Enterohepatic recirculation has been previously described; however, pharmacokinetics of the free and conjugated silybin is poorly studied [1]. To characterise bioavailability of silybin from 3TabGum and to better understand its enterohepatic recirculation we studied pharmacokinetics of the free and conjugated silybin in a group of healthy volunteers. Methods: Fifteen subjects provided 90 blood samples (6 per individual, range 0.5 to 5 h after administration). Total and free silybin A concentration has been determined by LC-MS. The population pharmacokinetic analysis was performed using NONMEM based on previously described quantitative enterohepatic circulation model [2]. Results: Oral clearance of silybin A was 600 L/h, oral volume of distribution was 57.2 L, absorption rate constant was 2.25 h-1, and absorption lag-time was 0.449 h. Elimination clearance of silybin A conjugates was 177 L/h, distribution volume was 12.5 L. 27.9% of silybin A conjugates entered into enterohepatic circulation with a period of sine function of 10.6 h and a shift of 2.69 h. Conclusion: The model adequately described multiple peaks in plasma concentration of Silybin A and was successfully applied for simultaneous evaluation of free and conjugated Silybin A pharmacokinetics. References: | |