Effect of glomerular filtration rate on clearance and myelotoxicity of carboplatin in cats with tumors

Objective-To characterize the pharmacokinetic disposition of carboplatin and determine whether glomerular filtration rate (GFR) could be used to predict carboplatin clearance and myelotoxic effects in cats with tumors. Animals-10 cats with tumors. Procedure-Glomerular filtration rate was assessed in each cat by monitoring plasma clearance of technetium Tc 99m-labeled diethylenetriaminepentaacetic acid (Tc-99m-DTPA). Each cat received carboplatin (200 mg/m(2) of body surface area) administered as an IV bolus. Plasma platinum concentrations were measured via atomic absorption spectrophotometry, and pharmacokinetic analysis was performed. A CBC was performed weekly for each cat, and the correlation between the area under the concentration-versus-time curve (AUC) and the severity of myelosuppression was calculated. Least squares regression analysis was performed to determine whether GFR could be used to predict plasma platinum clearance (Cl-Pt). Results-For all cats, AUC measurements ranged from 0.99 to 4.30 min(.)mg(.)mL(-1). Neutrophil concentration nadirs were detected 1 to 3 weeks after treatment and ranged from 200 to 8,000 cells/muL. The absolute neutrophil concentration at the nadir was inversely correlated with AUC. The Cl-Pt was predicted by use of GFR measurements (Cl-Pt = 2.60 X GFR). A carboplatin dose prescription model was derived involving AUC, estimated Cl-Pt, and body weight in kilograms (BWkg), in which dose = AUC X 2.60(GFR) X BWkg. Conclusions and Clinical Relevance-In cats, an individualized prescription strategy for carboplatin administration based on a targeted AUC and determination of GFR might more uniformly predict myelosuppression than that predicted by conventional dosing based on body surface area.