Population pharmacokinetics and individual analysis of daptomycin in kidney transplant recipients

Background: Little is known about the population pharmacokinetics (PPK) of daptomycin in kidney transplant patients. The present study established a pharmacokinetic model for daptomycin in kidney transplant patients in China and examinee the important factors affecting the pharmacokinetic parameters of daptomycin. Methods: The study population included 49 kidney transplant patients with 537 daptomycin concentrations. The PPK model of daptomycin was developed using a nonlinear mixed-effects model, a two-compartment structural model, and a mixed residual error model. The stability and predictive ability of the final model were evaluated based on bootstrapping, visual prediction checks and normalized prediction distribution errors. Results: Glomerular filtration rate (GFR) and total body weight significantly affected clearance, and body weight influenced the central volume of distribution. The average clearance of the population was 0.316 L/h, the central volume of distribution was 6.04 L, the intercompartmental clearance was 2.31 L/h, and the peripheral volume of distribution was 2.46 L. Based on the established model and the target of area under curve (AUC0-24h)/ minimum inhibition concentration (MIC) >= 666, we developed a recommended dose regimen for kidney transplant patients according to their renal function and weight. The daily doses were 4.0 +/- 0.31, 4.7 +/- 0.36, 5.1 +/- 0.40, 5.5 +/- 0.43, 5.8 +/- 0.45, and 6.1 +/- 0.48 mg/kg when the GFRs were 15, 30, 45, 60, 75, and 90 ml/min/1.73 m2, respectively. Conclusion: This study provides a reference for individualized daptomycin administration in kidney transplant recipients, and it is a valuable resource for improving the treatment effect and reducing the toxic effects of daptomycin.