Limited Sampling Strategy of Rosuvastatin Single-Time-point Concentrations Accurately Estimate Exposure and Constitutive Transporter Activities in Healthy Adults

Background: Rosuvastatin is commonly used as an exogenous probe drug to evaluate the activities of organic anion–transporting polypeptide (OATP) 1B1/3 and breast cancer resistance protein (BCRP). The authors evaluated a limited sampling strategy for rosuvastatin plasma concentrations to estimate exposure and potential OATP1B1/3 and BCRP activities. Methods: Plasma concentration versus time data were obtained from 36 healthy adults (8 women) from 2 published studies. Participants were administered a single oral dose (10 mg) of rosuvastatin under constitutive transporter conditions and concurrently with botanical goldenseal, green tea extract, or soy isoflavones. Backward stepwise linear regression generated single-time-point-limited sampling models (LSMs). Noncompartmental pharmacokinetic analysis was used to determine the area under the concentration versus time curve from time zero to the last measured concentration (AUC last ) from intensive sampling. No-effect boundary testing was performed to determine whether the LSMs reproduced the same outcome (i.e., presence or lack of interaction) as intensive sampling. Results: A 4-hour and 6-hour single-time-point concentration LSM accurately estimated the AUC last under constitutive OATP1B1/3 and BCRP conditions. Both rosuvastatin LSMs detected interactions with the green tea extract. Conflicting results regarding interactions with goldenseal and soy isoflavones were observed, with changes in exposure ranging from 11% to 14%. Conclusions: Limited sampling strategy of rosuvastatin concentrations accurately estimated AUC last during constitutive OATP1B1/3 and BCRP conditions but should be used with caution during altered transporter conditions.