Physiologically‐based pharmacokinetic modelling guided dose evaluations of nirmatrelvir/ritonavir in renal impairment for the management of COVID‐19

• Published in: British journal of clinical pharmacology Vol. 91; no. 4; pp. 1041 - 1048
• Main Authors: Ng, Tat Ming, Wang, Ziteng, Chan, Eric Chun Yong
• Format: Journal Article
• Language: English
• Published: England 01.04.2025
• Subjects: Antiviral Agents - administration & dosage; Antiviral Agents - pharmacokinetics; COVID-19 Drug Treatment; COVID‐19; Cytochrome P-450 CYP3A - metabolism; Dose-Response Relationship, Drug; dosing adjustment recommendation; Drug Combinations; Female; Humans; Male; Microsomes, Liver - metabolism; Middle Aged; Models, Biological; nirmatrelvir/ritonavir; physiologically‐based pharmacokinetic model; Renal Insufficiency - complications; Renal Insufficiency - metabolism; Ritonavir - administration & dosage; Ritonavir - pharmacokinetics; severe renal impairment; nirmatrelvir/ritonavir; COVID‐19; severe renal impairment; dosing adjustment recommendation; physiologically‐based pharmacokinetic model

We aimed to address factors contributing to the pharmacokinetic changes of nirmatrelvir/ritonavir in renal impaired (RI) patients and recommend dosing adjustment via a physiologically‐based pharmacokinetic (PBPK) modelling approach. A PBPK model of nirmatrelvir/ritonavir was developed via Simcyp® Si...