Pharmacokinetic study of carboplatin given on a 5-day intravenous schedule

We investigated whether carboplatin pharmacokinetics is altered when the drug is delivered daily over 5 days, compared to a single-day infusion. Carboplatin was infused in 11 patients with lung cancer, who were randomly assigned to 2 groups. In the first group, the agent was administered on a conventional single-day schedule in the first course and then on a 5-day schedule in the second course. In the second group, the order was reversed (crossover design). The dose was calculated using Calvert's formula with 24 h creatinine clearance (Ccr, ml/min) as a substitute for glomerular filtration rate (GFR): carboplatin (mg) = AUCx(Ccr+25), where AUC denotes the area under the concentration versus time curve (mg ml-1 min). No difference of carboplatin clearance between the single-day and 5-day schedule was observed (94.8 +/- 19.9 versus 96.1 +/- 29.9 ml/min, P = 0.818, paired t test). The formula systematically overestimated the carboplatin clearance: the ratio of estimated clearance/ observed clearance ranged from 1.01 to 1.58 (median 1.28; 95% confidence interval, 1.18 to 1.39). We concluded that the individual dosing strategy based on renal function can be applied with a 5-day schedule as well as a single-day schedule. Carboplatin is overdosed when Ccr is substituted for GFR in Calvert's formula.