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.
Ando
Y
Y
First Department of Internal Medicine, Nagoya University School of Medicine.
Minami
H
H
Saka
H
H
Ando
M
M
Sugiura
S
S
Sakai
S
S
Shimokata
K
K
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
D000970:Antineoplastic Agents; D016190:Carboplatin