Pharmacokinetic Study of Carboplatin Using Various Overweight-Correcting Dosing Algorithms and Biomarkers in Patients With Varying BMI Categories

Background: – The Cockcroft–Gault (CG) formula is more likely to overestimate renal function and carboplatin dosing in patients who are overweight. In this prospective pharmacokinetic study, the use of an adjusted Cockcroft–Gault formula (aCG) was evaluated to correct for overweight status.Methods: – aCG was adjusted in patients with body mass index (BMI) >25 kg/m ² using adjusted ideal body weight, capping low serum creatinine values at 60 μmol/L, and high creatinine clearance values at 125 mL/min. Patients were categorized as follows: BMI <25.0 (normal weight), 25.0–29.9 (overweight), and ≥30.0 kg/m ² (obese). To assess the pharmacokinetics, blood samples were collected and carboplatin ultrafiltrate concentrations were analyzed. Exposure was estimated using a population pharmacokinetic model and compared with the target area under the curve (AUC) regarding bias mean prediction error (MPE%) and imprecision mean absolute prediction error (MAPE%). In addition, substitutes for renal function, including weight descriptors, cystatin C, 24-hour creatinine clearance, and glomerular filtration rate estimators, were compared.Results: – Eighteen patients were included in this study. aCG slightly underestimated individual carboplatin clearance across all weight groups, with the highest deviation in patients who had obesity (MPE%: −10.5%) versus +8.8% using CG. aCG underestimated −5.7% in patients with a normal weight and overestimated by +1.1% in those who were overweight, compared with −4.2% and +2.8%, respectively, using CG. The most accurate predictor of the target AUC for all weight categories was cystatin C (MPE%: +0.2%, −2.0%, and −0.1% for patients with a normal weight, those who were overweight, and those who had obesity, respectively) with low imprecision (MAPE%: 9.8%, 9.5%, and 13.3%, respectively).Conclusions: – This study did not find evidence to support using aCG to predict carboplatin clearance better than CG. However, cystatin C was found to be the most precise and accurate biomarker for carboplatin clearance.