Pharmacokinetics and pharmacodynamics of nitrosourea fotemustine: a French cancer centre multicentric study.
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.
Iliadis
A
A
Faculté de Pharmacie, Marseille, France.
Launay-Iliadis
M C
MC
Lucas
C
C
Fety
R
R
Lokiec
F
F
Tranchand
B
B
Milano
G
G
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D009607:Nitrosourea Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000633:toxicity; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000633:toxicity; D011446:Prospective Studies; D013997:Time Factors
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; C054368:fotemustine