Population pharmacokinetics and dosing optimization of teicoplanin in renal transplant patients

The objectives of this study were to investigate the population pharmacokinetic (PK) characteristics of teicoplanin in renal transplant patients and to provide recommendations for optimal teicoplanin dosing regimens. A total of 99 renal transplant patients with 386 plasma samples were enrolled (306 in development and 80 in validation). A population PK analysis and simulations were performed to identify the optimal teicoplanin doses needed to provide an 80% probability of target attainment at 72 h and 168 h using both a trough concentration target of >15 µg/mL and the ratio of 24 h area under the concentration-time curve to the minimum inhibitory concentration >610.4. Teicoplanin was well described by a two-compartment PK model. The final model parameter estimates for clearance, central compartment volume of distribution, intercompartmental clearance, and peripheral compartment volume were 0.711 L/h, 11.3 L, 4.22 L/h, and 35.2 L, respectively. Creatinine clearance (CrCL) was the only covariate that significantly affected teicoplanin clearance. Dosing simulation results showed that standard dosing regimens were unable to meet the treatment needs of all patients, and CrCL-based individual dosing regimens are recommended for both loading dose and maintaining dose. Higher-than-standard teicoplanin doses are necessary to achieve prompt and appropriate drug exposure in renal transplant patients.