Earlier Geuns et al. (2006) found steviol glucuronide in human
urine after stevioside administration. In further studies in human
subjects receiving stevioside orally at a dose of 750 mg/day for 3 days,
steviol glucuronide was the only metabolite found in blood and urine,
whereas no stevioside or steviol was detected (Geuns et al., 2007).
Analysis of feces found only free steviol and no stevioside or steviol
glucuronide, suggesting an additional route of steviol elimination. In a
recent randomized double-blind, crossover study, pharmacokinetics
of steviol glucuronide and free steviol in 8 healthy adult male subjects
receiving a single oral dose of rebaudioside A (5 mg/kg BW) or
stevioside (4.2 mg/kg BW) showed plasma steviol level of 121 ng/ml
after 6 h of administration (Wheeler et al., 2008). Steviol glucuronide
is present in plasma of all subjects following oral administration of
stevioside, with the median time to peak concentration of 8 h and
mean maximum concentration of 1.89 μg/ml. In urine, the majority of
steviol was found in the form of glucuronide conjugates (62% of dose)
with a much lower amount of free steviol (0.04% of dose). Thus, it
appears that, in addition to phase I metabolism, steviol undergoes
phase II metabolism in which the greater part of steviol is conjugated
with glucuronide before being eliminated in urine. This study also
suggests the involvement of a similar metabolic pathway for
rebaudioside A