Drug Design, Development and Therapy (Jun 2022)
Population Pharmacokinetics of Tigecycline: A Systematic Review
Abstract
Can-Can Zhou,1,* Fang Huang,1,* Jing-Ming Zhang,1 Yu-Gang Zhuang2 1Department of Pharmacy, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 2Department of Emergency Medicine, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu-Gang Zhuang, Email [email protected]: Although tigecycline is widely used in clinical practice, its efficiency and optimal dosage regimens remain controversial. The purpose of this article was to help guide tigecycline dosing in different patient subpopulations through comparing the published population pharmacokinetic models of tigecycline, as well as summarizing and determining the potential covariates that markedly influence tigecycline pharmacokinetics. In this review, literature was systematically searched from the PubMed database from inception to March 2022. The articles focusing on population pharmacokinetics for tigecycline in healthy volunteers or patients were included; finally, a total of eight studies were included in this review. NONMEM methods were used in five studies to generate the population pharmacokinetic models. Tigecycline pharmacokinetics were mostly described by a two-compartment model in these included studies. Estimated clearance and volumes of distribution of tigecycline at steady state (Vss) varied widely in different target patient populations, with a range of 7.5– 23.1 L/h and 212.7– 1087.7 L, respectively. Body-weight and creatinine clearance were the most important predictors of clearance in these studies, while other predictors include age, gender, bilirubin and aspartate aminotransferase. In conclusion, this review showed the large variability of tigecycline population pharmacokinetics, which can provide guide dosing in different target populations. For clinicians, the individual dosing adjustment should be based not only on the indication and pathogen susceptibility but also on the potential important predictors. However, more studies were needed to confirm the necessity of modified dosage regimens in different patient subpopulations.Keywords: tigecycline, population pharmacokinetics, modelling, NONMEM
