were the first to determine the pharmacokinetics
of stevioside after a single dose of oral administration of
3H-stevioside (125 mg/kg BW) into male Wistar rats. Maximal
radioactivity level in blood (4.8 μg/ml)was found at 8 h after stevioside
administration with an elimination half-life of 24 h. Analysis of
radioactivity levels in key organs and tissues demonstrated preferential
accumulation in small and large bowels. Following intravenous
injection of radioactive 131I-stevioside into Wistar male rats, radioactivity
in heart, stomach, testes and muscle is less than 1.8% of the
injected dose during the entire 24 h experiment (Cardoso et al., 1996).
However, a significant amount of radioactivity was detected in liver,
intestine and kidney. The accumulation in the liver is highest after
10 min of injection. Significant radioactivity is present in bile after
120 min, with an accumulative amount of 52% of the injected dose. Its
presence is maximal in small and large intestines after 120 and 240 min
following stevioside injection, respectively. High performance liquid
chromatography (HPLC) analysis of bile showed steviol as the major
metabolite.Whereas, urine analysis revealed the presence of stevioside
as a major component with a much less amount of an unknown
metabolite that was also found in the bile. These results indicate that
metabolic conversion of stevioside to steviol in rats occurs in liver and
there are two routes of stevioside excretion, via bile and urine. In
addition, steviol may undergo enterohepatic circulation where steviol
is excreted into bile and reabsorbed back to circulation. However, the
presence of steviol in portal venous systemwas not documented in the
study.