Category: Professional Posters
Purpose: Pharmacokinetics of cisplatin (CDDP) has not been investigated for patients with renal dysfunction and creatinine clearance (Ccr) of < 60 mL/min. In this study, we performed population pharmacokinetic analysis of CDDP in the patients with renal dysfunction, and investigated the effect of renal dysfunction on the pharmacokinetics of CDDP. Additionally, CDDP-induced nephrotoxicity was researched.
Methods: Twenty three patients (Ccr: 35.1-59.9 mL/min) were treated with CDDP (35-80 mg/m2) via intravenous constant infusion for 60 min. Blood samples were taken at 2-4 time points per patient. Population pharmacokinetic analysis was performed by nonlinear mixed effect modelling using NONMEM (Version 7.2). The final model was evaluated using nonparametric bootstrap analysis.
Results: A one-compartment structure model adequately described the CDDP data. The population mean values for CDDP clearance (CL) and distribution volume (Vd) were 19.1 L/h (%CV 19.4) and 13.8 L (%CV 41.0), respectively. In the final model, body surface area (BSA) was identified as a significant covariate for CL. However, no significant covariates were found for Vd. With regard to the nephrotoxicity, no one experienced severe renal dysfunction wherein serum creatinine (Scr) was increased to grade 3 or 4.
Conclusion: Renal dysfunction does not affect the pharmacokinetics of CDDP. The dose adjustment of CDDP due to renal dysfunction may not be necessary for pharmacokinetics.