Background: Over the past two decades, saccharolactone has been routinely used in in vitro microsomal
incubations, and sometimes in incubations with recombinant Uridine diphosphoglucuronosyl transferases (UGT)
while investigating glucuronidation reactions. The addition of saccharolactone is aimed at completely inhibiting β-
glucuronidases that may be present in the microsomes, in the anticipation of accurate identification and quantification
of the formed glucuronide metabolites. Recent research has demonstrated that saccharolatone may not serve the intended
objective, and may even lead to inhibition of certain UGTs.
Objective: This report investigates the historic evidence in the practice of saccharolactone addition in relation to β-glucuronidases and UGTs. The chemical nature and inhibition potency of saccharolactone are explored in an attempt to
unravel the myth in its application. Finally, the collective evidence is discussed in an effort to provide guidance to drug
metabolism scientists on the utilization of saccharolactone.
Conclusion: In-depth evaluation of the experimental evidence in the literature points toward a weak rationale for general
in vitro application of saccharolactone. Furthermore, inhibition of recombinant or microsomal UGTs by saccharolactone
may be model dependent. Overall, the integrated data suggests that saccharolactone should not be utilized in in vitro
microsomal incubations with the objective of inhibiting β-glucuronidases.