A Systematic Review of Population Pharmacokinetics, Safety, and Factors Influencing Trough Concentrations of Voriconazole in Asian Patients with Liver Dysfunction

Lin Hu,1,2 Changyu Wang,3 Shiqiong Huang,1,2 Xi Tang,1,2 Yanfei Li1,2 1Department of Pharmacy, the Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Pharmacy, the First Hospital of Changsha, Changsha, Hunan, People’s Republic of China; 3School of Mathematics and Physics, Wenzhou University, Wenzhou, Fujian, People’s Republic of ChinaCorrespondence: Yanfei Li, Email [email protected] Lin Hu, Email [email protected]: This study systematically reviews recent research on voriconazole (VRC) use in Asian patients with liver dysfunction to provide a scientific basis for individualized therapy.Methods: A comprehensive literature search was conducted in EMBASE, PubMed, Web of Science, and the Cochrane Library for clinical studies on VRC use in Asian patients with liver dysfunction, published between January 1, 2000, and March 1, 2025. Studies meeting the inclusion and exclusion criteria were analyzed to summarize VRC safety, factors influencing trough concentrations (Ctrough), pharmacokinetic characteristics, and advancements in dose optimization.Results: A total of 14 studies were included, comprising 9 studies on the safety of VRC in patients with liver dysfunction, 5 studies investigating factors affecting VRC Ctrough, and 6 studies on population pharmacokinetics (PPK) in this population. The most commonly reported adverse drug reactions (ADRs) related to VRC were hepatotoxicity, neurotoxicity, and visual impairment. ADRs typically occurred within 7 days of VRC administration. VRC Ctrough are influenced by several factors, including liver impairment severity, CYP2C19 polymorphisms, and albumin and bilirubin levels. The PPK models assessed clearance (CL) in patients with different Child-Pugh (CP) classifications, all of which showed a significant reduction in CL among CP-C patients. Regarding the elimination half-life (t₁/2), CP-C patients exhibited a significant prolongation.Conclusion: Therapeutic drug monitoring (TDM) and PPK studies can aid in optimizing VRC dosing, ensuring safer and more effective individualized therapy.Keywords: voriconazole, liver dysfunction, population pharmacokinetics, safety, trough concentrations