Population pharmacokinetics and individual analysis of daptomycin in kidney transplant recipients

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.

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.

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 (AUC_0-24h)/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.

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.