VALIDATION OF A LIMITED SAMPLING MODEL FOR CARBOPLATIN IN A HIGH-DOSECHEMOTHERAPY COMBINATION

Citation
Ljc. Vanwarmerdam et al., VALIDATION OF A LIMITED SAMPLING MODEL FOR CARBOPLATIN IN A HIGH-DOSECHEMOTHERAPY COMBINATION, Cancer chemotherapy and pharmacology, 35(2), 1994, pp. 179-181
Citations number
7
Language
INGLESE
art.tipo
Note
Categorie Soggetti
Pharmacology & Pharmacy",Oncology
ISSN journal
0344-5704
Volume
35
Issue
2
Year of publication
1994
Pages
179 - 181
Database
ISI
SICI code
0344-5704(1994)35:2<179:VOALSM>2.0.ZU;2-I
Abstract
A limited sampling model for the estimation of the carboplatin area un der the concentration versus time curve (AUC), as developed by Sorense n et al., was validated prospectively for the use in a high-dose combi nation chemotherapy schedule. The model allows an estimation of the AU C on the basis of only one timed plasma drug concentration, sampled at exactly 2.75 h after a 1-h carboplatin infusion. Pharmacokinetic curv es were obtained from nine patients receiving carboplatin (400 mg/m(2) per day) combined with cyclophosphamide (1500 mg/m(2) per day), thiot epa (120 mg/m(2) per day), and mesna (3 g/day) for 4 consecutive days. Peripheral blood stem-cell transplantation (PBSCT) was performed 3 da ys later to restore hematopoiesis. Using this combination of high dose s, the model proved to be unbiased (MPE -3.40%; SE, 1.22%) and highly precise [root mean squared prediction error (RMSE), 5.15%; SE, 0.17%] for estimation of the AUC during 4 consecutive days. The validated lim ited sampling model provides a starting point for future pharmacokinet ic studies in a larger population of patients, which might lead to mor e insight into the relationships with the pharmacodynamic outcome of c arboplatin and may help in achieving more rational dosing of patients on the basis of an AUC determination.