ADJUSTMENT OF CREATININE CLEARANCE IMPROVES ACCURACY OF CALVERTS FORMULA FOR CARBOPLATIN DOSING

Carboplatin clearance depends on the glomerular filtration rate (GFR), and Calvert's formula is frequently used to achieve a target area und er the time vs concentration curve (mg ml(-1) min). Creatinine clearan ce is a substitute for GFR when creatinine Values are determined by th e Jaffe method, which is being replaced by the enzymatic method. When the enzymatic method is used, the corresponding creatinine clearance t heoretically exceeds GFR, and the use of creatinine clearance as GFR i n Calvert's formula results, accordingly, in overdosing of carboplatin . In this study, we have established a model for adjusting the creatin ine clearance to offset this bias based on a relationship between crea tinine values measured by the Jaffe method and by the enzymatic method : adjusted creatinine clearance (ml min(-1)) = creatinine clearance (m i min(-1)) x [serum creatinine (mg dl(-1))]/[serum creatinine (mg dl(- 1)) + 0.2]. Subsequently, we Validated this model using the data from 35 lung cancer patients. Estimated clearances of carboplatin with the original equation [creatinine clearance + 25] were systematically high er than observed clearances [mean prediction error (MPE) +/- standard error (s.e.) = 26 +/- 5%]. This positive bias was corrected by the adj ustment (MPE +/- s.e. = 5 +/- 4%). When the enzymatic method is used, the adjusted creatinine clearance should be used in Calvert's formula.