Endogenous plasma riboflavin is not a viable BCRP biomarker in human

Recent reports suggest that plasma riboflavin may serve as a biomarker for BCRP inhibition in humans. However, the clinical data supporting this claim have been limited, with only two studies showing modest increases in riboflavin levels after administration of a BCRP inhibitor. We have recently demonstrated that co-administration of 375 mg once daily (q.d.) cedirogant, an in vitro BCRP inhibitor, significantly increased rosuvastatin (an OATP1B1/1B3 and BCRP substrate) exposures but did not change the levels of the OATP1B endogenous biomarker coproporphyrin-I, demonstrating that cedirogant is a clinical BCRP inhibitor. Samples from this same cedirogant clinical drug–drug interaction study were utilized to test the hypothesis that endogenous plasma riboflavin is a biomarker of BCRP inhibition. Plasma riboflavin levels in the absence of cedirogant ranged from 1 to 10 ng/mL across the 11 participants analyzed with minimal (<20%) intrasubject variability over a 24-hour interval. Contrary to expectations, 375 mg q.d. oral administration of cedirogant did not increase riboflavin levels. These data strongly suggest that endogenous plasma riboflavin is not a viable biomarker for BCRP inhibition in humans.