AIM: The inhibition of organic anion transporting polypeptide 1B1 (OATP1B1) on the pharmacokinetics of rosuvastatin is unknown. Hence, the effect of ursodeoxycholic acid (UDCA) on the kinetics of rosuvastatin in healthy volunteers is to be investigated. METHODS: The inhibition effect of long term use of UDCA on rosuvastatin kinetics was studied in 12 subjects in a randomized, crossover study. Each subject received 500 mg UDCA once daily continuously for 14 days. A single oral dose of 20 mg rosuvastatin was given on study day 15 and 34 separated by 2 weeks. Plasma concentrations of rosuvastatin were above the limits of quantitation for up to 72 h after dosing. RESULTS: UDCA significantly increased AUC0-72 and AUC0-∞ of rosuvastatin to 146%±55% (P=0.008) and 167%±73% (P=0.004) compared with those of the control group and CL/F decreased 75%±19% (P=0.003). The results confirmed the in vitro study that UDCA inhibited OATP1B1 activity via hepatic nuclear factor 1a (HNF1a). CONCLUSION: Inhibition of HNF1a and hepatic uptake may have consequences on clinic outcomes of drugs like rosuvastatin mainly excreted by hepatobiliary system.
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