An Update on Population Pharmacokinetic Analyses of Vancomycin, Part I: In Adults.

Abstract

Despite the wide clinical use of vancomycin, controversy remains regarding its optimal dosage regimens. This can be attributed to the large between- and within-subject variability in the pharmacokinetics of vancomycin. This review aimed at providing a synthesis of population pharmacokinetic models of vancomycin in adults, determining the most reported pharmacokinetic models, and identifying various sources of variability in different special subpopulations to better inform vancomycin dosing. We searched PubMed and EMBASE for population pharmacokinetic studies of vancomycin published from January 2011 to May 2019. Inspection of the relevant lists of references was conducted, as well. This search resulted in a total of 30 eligible studies, which were included. One-, two-, and three-compartments models were reported to best describe vancomycin population pharmacokinetics in 13, 14, and 3 studies, respectively. Three-compartment models were implemented in three studies to account for an additional cerebrospinal fluid compartment. The most common predictors were creatinine clearance and bodyweight, in 20 and 13 studies, respectively. Estimated values of vancomycin clearance and total volume of distribution varied widely from 0.334 to 8.75 L/h (0.0054-0.1279 L/h/kg) and from 7.12 to 501.8 L (0.097-6.97 L/kg), respectively. Almost all studies implemented an exponential interindividual variability model, and the highest variability on clearance was 99.2%. In conclusion, this review highlights the wide ranges and the high variability of estimated population pharmacokinetic parameters. This information can help guide dosing in different subpopulations. Yet, additional analyses with pooled subpopulations might be needed to confirm the necessity of modified dosage regimens.