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

Abstract

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 (99mTc-DTPA). Each cat received carboplatin (200 mg/m2 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 (ClPt). RESULTS: For all cats, AUC measurements ranged from 0.99 to 4.30 min x mg x mL(-1). Neutrophil concentration nadirs were detected 1 to 3 weeks after treatment and ranged from 200 to 8,000 cells/microl. The absolute neutrophil concentration at the nadir was inversely correlated with AUC. The ClPt was predicted by use of GFR measurements (ClPt = 2.60 x GFR). A carboplatin dose prescription model was derived involving AUC, estimated ClPt, 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.