Pharmacokinetic analysis of carboplatin in patients with cancer who are undergoing hemodialysis.
OBJECTIVE
To examine the safety of carboplatin-based chemotherapy and the applicability of the Calvert formula in patients with cancer who are undergoing hemodialysis.


METHODS
We treated two patients who were undergoing hemodialysis and received carboplatin-based chemotherapy to treat non-small-cell lung cancer or ovarian cancer. The dose of carboplatin was calculated by the Calvert formula. Glomerular filtration rate was considered to be 0, and the target area under the plasma concentration versus time curve (AUC) was 4 (carboplatin dose, 100 mg) for patient 1 and 5 (125 mg) for patient 2. Carboplatin was administered as a 1-h intravenous infusion on day 1. Hemodialysis was performed for 3 or 4 h, starting 24 h after the infusion of carboplatin had begun. Heparinized blood samples were collected during the first cycle of chemotherapy.


RESULTS
The AUCs in patients 1 and 2 were 4.7 and 6.1 (mg/ml min), which were about 20% higher than the target values (4 and 5 mg/ml min, respectively). In the absence of hemodialysis, the hypothetical AUCs were 6.2 and 7.6 (mg/ml min), respectively. The pre-dialysis body clearances of carboplatin were 16.1 and 16.5 ml/min, with elimination half-lives of 17.5 and 13.8 h, respectively.


CONCLUSIONS
By performing hemodialysis 24 h after the start of chemotherapy, we obtained reproducible and robust AUC data. Use of the Calvert formula allowed carboplatin-based chemotherapy to be performed safely. Our results suggest that the non-renal clearance of carboplatin is lower in Japanese patients than in non-Asian patients.
Oguri
Tomoyo
T
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan.
Shimokata
Tomoya
T
Inada
Megumi
M
Ito
Isao
I
Ando
Yuichi
Y
Sasaki
Yasutsuna
Y
Hasegawa
Yoshinori
Y
D000465:Algorithms; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D016190:Carboplatin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism; D006435:Renal Dialysis
D000970:Antineoplastic Agents; D016190:Carboplatin