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
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.