Pharmacokinetics and pharmacodynamics of nitrosourea fotemustine: a French cancer centre multicentric study.
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| Abstract |
The nitrosourea, fotemustine, was given intravenously in 1 h constant-rate infusion to 66 patients in a multicentric study to assess both fotemustine pharmacokinetic behaviour and the pharmacokinetic-pharmacodynamic relationships. Depending on the tumour type treated, two administration and sampling protocols were used: 100 mg/m2/week as a conventional dose (six samples, 44 patients) and 300-500 mg/m2/day as a high dose (10 samples, 22 patients). The 91 time-concentration curves were best described by either a one-(55) or a two-compartment (36) model, and their mean clearance values did not differ significantly (85.3 +/- 6.5 and 101.3 +/- 9.5 l/h, respectively, P = 0.1727). Fotemustine pharmacokinetics were not influenced by repeated treatment (time-independence) nor by dose level (dose-independence). The pharmacodynamic effect observed on white blood cell count was expressed by a logit regression model involving the area under the curve mainly and the total administered dose. White blood cell toxicity could be predicted as a function of the dose for a given patient with a known fotemustine clearance value.
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| Authors | A Iliadis, M C Launay-Iliadis, C Lucas, R Fety, F Lokiec, B Tranchand, G Milano |
| Journal | European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 32A Issue 3 Pg. 455-60 (Mar 1996) ISSN: 0959-8049 [Print] England |
| PMID | 8814692 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't) |
| Chemical References |
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