Physiologically based pharmacokinetic modeling of ritonavir-oxycodone drug interactions and its implication for dosing strategy

• DOI: 10.1016/j.ejps.2024.106697
• Publication Date: 2024-01-08T16:48:36Z
• Authors: Liang Zheng; Wei Zhang; Klaus T. Olkkola; André Dallmann; Liang Ni; Yingjie Zhao; Ling Wang; Qian Zhang; Wei Hu
• Keywords: Ritonavir; Pharmacodynamics

The concomitant administration of ritonavir and oxycodone may significantly increase the plasma concentrations oxycodone. This study was aimed to simulate DDI between oxycodone, a widely used opioid, formulate dosing protocols for by using physiologically based pharmacokinetic (PBPK) modeling. We developed PBPK model incorporating induction competitive time-dependent inhibition CYP3A4 CYP2D6. evaluated with observed clinical data validated its potency. then drug interactions under various scenarios. captured characteristics from studies. also accurately predicts exposure changes midazolam, triazolam, in presence ritonavir. According simulations, steady-state maximum, minimum average increased up 166% after co-administration ritonavir, total approximately 120%. To achieve similar concentrations, halving dose an unchanged interval or doubling unaltered single should be practical whether formulated uncoated controlled-release tablets during long-term co-medication results revealed exposure-related risks oxycodone-ritonavir that have not been studied clinically emphasized as workable method direct judicious dosage.