Pharmacokinetics and metabolism of siamenoside I in rats

The pharmacokinetics and metabolism of [¹⁴C]-siamenoside I were studied following single oral doses of 5 mg/kg bodyweight with intact and bile duct-cannulated rats. Elimination of radioactivity was rapid and essentially complete by the end of the sample collection period (0-168 h), with the primary excretion route being the feces (101 % males and 92 % females). The estimate of absorption determined from the level of radiolabel in the bile of bile duct-cannulated rats was approximately 43 % in males and 42 % in females. The resultant systemic exposure as determined via urinary as well as blood and plasma radioactivity levels was low relative to the administered dose with only 1-1.5 % eliminated in intact and bile duct-cannulated male and female urine. Blood, plasma and tissue radioactivity levels were rapidly and widely distributed with the overall distribution low relative to administered dose. Metabolism of siamenoside I, to mogrol following cleavage of the sugar groups was the major component of feces (53-59 %), which appears to occur in the gastrointestinal tract prior to absorption. This was supported by mogrol being a significant component of radioactivity in plasma and tissues. The biotransformation of absorbed radioactivity also involved formation of several oxidized metabolites of mogrol, generally addition of oxygen and/or dehydrogenation. Overall absorption and subsequent excretion of [¹⁴C]-siamenoside I was similar in male and female rats as determined by the levels of radioactivity present in the urine and bile with no evidence of accumulation or retention observed in any tissue.