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Physiologically ‐Based Pharmacokinetic Modeling for the Prediction of a Drug–Drug Interaction of Combined Effects on P‐glycoprotein and Cytochrome P450 3A
Direct oral anticoagulants, such as apixaban and rivaroxaban, are important for the treatment and prophylaxis of venous thromboembolism and to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Because apixaban and rivaroxaban are predominantly eliminated by cytochrome P450 (CYP) 3A and P ‐glycoprotein (P‐gp), concomitant use of combined P‐gp and strong CYP3A4 inhibitors and inducers should be avoided. Physiologically‐based pharmacokinetic models for apixaban and rivaroxaban were developed to estimate the net effect of CYP3A induction, P‐gp inhibition, and P‐gp ind...
Source: CPT: Pharmacometrics and Systems Pharmacology - November 12, 2020 Category: Drugs & Pharmacology Authors: Yukio Otsuka, Mary P. Choules, Peter L. Bonate, Kanji Komatsu Tags: Article Source Type: research

Physiologically ‐based Pharmacokinetic Modeling for the Prediction of a Drug‐Drug Interaction of Combined Effects on P‐gp and CYP3A
AbstractDirect oral anticoagulants, like apixaban and rivaroxaban, are important for the treatment and prophylaxis of venous thromboembolism and to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Since apixaban and rivaroxaban are predominantly eliminated by CYP3A and P ‐glycoprotein (P‐gp), concomitant use of combined P‐gp and strong CYP3A4 inhibitors and inducers should be avoided. Physiologically‐based pharmacokinetic (PBPK) models for apixaban and rivaroxaban were developed to estimate the net effect of CYP3A induction, P‐gp inhibition and P‐gp indu ction by...
Source: CPT: Pharmacometrics and Systems Pharmacology - October 8, 2020 Category: Drugs & Pharmacology Authors: Yukio Otsuka, Mary P. Choules, Peter L. Bonate, Kanji Komatsu Tags: ARTICLE Source Type: research