Population pharmacokinetics of levofloxacin: a systematic review

Levofloxacin is an effective anti-infective agent for the treatment of infectious diseases. However, the marked interindividual variability in levofloxacin pharmacokinetics (PKs) across different populations introduces uncertainty regarding its clinical efficacy and safety. This review aims to comprehensively summarize population pharmacokinetic (PopPK) studies of levofloxacin and to elucidate the covariates that significantly influence its PKs. PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were searched from database inception to October 2025. A total of 20 studies from 15 countries were finally included and PopPK data were extracted. One-compartment and two-compartment models were applied in 12 and 8 studies, respectively. The estimated weight-normalized clearance (CL) of levofloxacin varied widely, ranging from 0.07 L/h/kg to 0.39 L/h/kg, with a median value of 0.13 L/h/kg. Pediatric patients appeared to clear levofloxacin faster than adults, whereas the elderly exhibited the slowest CL. The most frequently identified covariates affecting levofloxacin CL were renal function, age, weight, pregnancy, and human immunodeficiency virus infection status. The variability in volume of distribution was primarily explained by weight, gender, and aspartate aminotransferase. Large, multicenter, and prospective PopPK studies are warranted to elucidate the PKs of levofloxacin, thus facilitating model-informed precision dosing in clinical practice. This review provides a valuable reference for the future development of PopPK analysis for levofloxacin.