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• W2896684385 abstract "Background: Therapeutic drug monitoring of carboplatin is based on its unbound clearance (CL U ) determined by Bayesian analysis on unbound (U) concentrations. However, the ultrafiltration of plasma samples presents technical and time constraints. Therefore, this study aims to estimate CL U using total plasma (P) concentrations. Methods: U and P concentration data of 407 patients were obtained from 2 clinical studies in which actual CL U had been determined for each patient. The patients were then split into development (277 patients) and prospective data sets (130 patients). Two approaches were evaluated. PK-model-only approach : a 3-compartment pharmacokinetic (PK) model based on U and P concentrations and taking into account the protein binding process was developed. The model with patient covariates was also evaluated. Linear regression approach : an equation (CL U = aCL P + b) was obtained by linear regression analysis between actual CL U and CL P, which is the total plasma clearance obtained by analyzing P concentrations according to a 2-compartment PK model. Predictive performance was then assessed within the prospective data set by estimating CL U from P concentrations using each approach and computing the relative percentage error (PE) between estimated CL U and actual CL U . Results: The linear regression equation was CL U (L/h) = 1.15 CL P (L/h) + 0.13. The mean PE (MPE) between CL U (estimated using the equation) and the actual CL U was +1.2% (ranging from −31% to +33%) and the mean absolute PE (MAPE) was 9.7%. With the 3-compartment PK model, the MPE was +2.3% (ranging from −41% to +31%) and the MAPE was 11.1%. Inclusion of covariates in the 3-compartment model did not improve the estimation of CL U [MPE = +6.3% (from −33% to +37%); MAPE = 11.4%]. Conclusions: The linear equation gives a relatively good estimation of CL U based on P concentrations, making PK-based carboplatin dose adaptation possible for centers without ultrafiltration facilities." @default.
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• W2896684385 date "2019-02-01" @default.
• W2896684385 modified "2023-10-14" @default.
• W2896684385 title "Estimation of Unbound Carboplatin Clearance From Total Plasma Concentrations as a Means of Facilitating Therapeutic Drug Monitoring" @default.
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• W2896684385 doi "https://doi.org/10.1097/ftd.0000000000000569" @default.
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