Y. Ando et al., PHARMACOKINETIC STUDY OF CARBOPLATIN GIVEN ON A 5-DAY INTRAVENOUS SCHEDULE, Japanese journal of cancer research, 88(5), 1997, pp. 517-521
We investigated whether carboplatin pharmacokinetics is altered when t
he drug is delivered daily over 5 days, compared to a single-day infus
ion. Carboplatin was infused in 11 patients with lung cancer, who were
randomly assigned to 2 groups. In the first group, the agent was admi
nistered 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, t
he order was reversed (crossover design). The dose was calculated usin
g Calvert's formula with 24 h creatinine clearance (Cer, ml/min) as a
substitute for glomerular filtration rate (GFR): carboplatin (mg) = AU
C x (Cer + 25), where AUC denotes the area under the concentration ver
sus 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 s
ystematically overestimated the carboplatin clearance; the ratio of es
timated 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 in
dividual dosing strategy based on renal function can be applied with a
5-day schedule as well as a single-day schedule. Carboplatin is overd
osed when Cer is substituted for GFR in Calvert's formula.