Beschreibung:
<jats:title>Abstract</jats:title><jats:p><jats:bold>Objective</jats:bold>—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.</jats:p><jats:p><jats:bold>Animals</jats:bold>—10 cats with tumors.</jats:p><jats:p><jats:bold>Procedure</jats:bold>—Glomerular filtration rate was assessed in each cat by monitoring plasma clearance of technetium Tc 99m-labeled diethylenetriaminepentaacetic acid (<jats:sup>99m</jats:sup>Tc-DTPA). Each cat received carboplatin (200 mg/m<jats:sub>2</jats:sub>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<jats:sub>Pt</jats:sub>).</jats:p><jats:p><jats:bold>Results</jats:bold>—For all cats, AUC measurements ranged from 0.99 to 4.30 min·mg·mL<jats:sup>–1</jats:sup>. Neutrophil concentration nadirs were detected 1 to 3 weeks after treatment and ranged from 200 to 8,000 cells/µL. The absolute neutrophil concentration at the nadir was inversely correlated with AUC. The Cl<jats:sub>Pt</jats:sub>was predicted by use of GFR measurements (ClPt = 2.60 × GFR). A carboplatin dose prescription model was derived involving AUC, estimated Cl<jats:sub>Pt</jats:sub>, and body weight in kilograms (BW<jats:sub>kg</jats:sub>), in which dose = AUC × 2.60(GFR) × BW<jats:sub>kg</jats:sub>.</jats:p><jats:p><jats:bold>Conclusions and Clinical Relevance</jats:bold>—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. (<jats:italic>Am J Vet Res</jats:italic>2004;65:1502–1507)</jats:p>