PREDICTION OF CARBOPLATINE CLEARANCE FROM MORPHOLOGICAL AND BIOLOGICAL PATIENT CHARACTERISTICS

Hematologic toxicity of carboplatin is largely dependent on its pharma cokinetics. Its seems likely that therapeutic efficacy is also related to plasma drug exposure. Dosage adjustments based on isotopic determi nation of glomerular filtration rate have been proposed but their ambu latory use is not conceivable. A population pharmacokinetic study was undertaken to determine a relationship between patient characteristics and carboplatin clearance. Plasma carboplatin pharmacokinetics were d etermined as ultrafilterable platinum in 70 patients (23 to 84 years o ld) treated with different combination regimens including carboplatin at doses ranging from 184 to 950 mg (1-hr iv infusion) for various tum or types. Data were analysed using Nonlinear Mixed Effects Model (NONM EM). The data from 34 patients (46 cycles) were used to obtain the mos t predictive formula for the carboplatin clearance (ml/min): 0.134 wei ght + 218 weight (1 -0.00457 x age) (1 -0.314 sex)/ creatinine(mu M) T he obtained formula was prospectively evaluated with the data from 36 other patients (43 cycles) and compared to other methods available to predict carboplatin clearance. Prospectively this formula predicted th e clearance with a good precision (median absolute percent error of 10 % range 0-30%) and minimal bias (median percent error: 2% range -25-30 %). This method of prediction was as accurate as the one which require s the glomerular filtration rate to be measured by 51Cr-EDTA injection . This formula should allow to individualize very easily the carboplat in dosage in adults by multiplying the calculated carboplatin clearanc e by the area under the curve desired for administration [J Natl Cance r Inst 1995;87:573-80].