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Transl Clin Pharmacol. 2016 Mar;24(1):55-62. English. Original Article.
Park WS , Jang D , Han S , Yim DS .
Department of Clinical Pharmacology and Therapeutics, Seoul St. Mary's Hospital, PIPET (Pharmacometrics Institute for Practical Education and Training), College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.

The Cmax and AUC of rosuvastatin increase when it is coadministered with telmisartan. The aim of this study was to explore which of the pharmacokinetic (PK) parameters of rosuvastatin are changed by telmisartan to cause such an interaction. We used data from drug–drug interaction (DDI) studies of 74 healthy volunteers performed in three different institutions. Rosuvastatin population PK models with or without telmisartan were developed using NONMEM (version 7.3). The plasma concentration–time profile of rosuvastatin was best described by a two-compartment, first-order elimination model with simultaneous Erlang and zero-order absorption when given rosuvastatin alone. When telmisartan was coadministered, the zero-order absorption fraction of rosuvastatin had to be omitted from the model because the absorption was dramatically accelerated. Notwithstanding the accelerated absorption, the relative bioavailability (BA) parameter estimate in the model demonstrated that the telmisartan-induced increase in BA was only about 20% and the clearance was not influenced by telmisartan at all in the final PK model. Thus, our model implies that telmisartan may influence the absorption process of rosuvastatin rather than its metabolic elimination. This may be used as a clue for further physiologically based PK (PBPK) approaches to investigate the mechanism of rosuvastatin–telmisartan DDI.

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