D. Godeneche et al., PHARMACOKINETICS OF 2 NEW 2-CHLOROETHYLNITROSOUREAS IN CANCER-PATIENTS SUBMITTED TO PHASE-II CLINICAL-TRIALS, Drug investigation, 7(5), 1994, pp. 234-243
The pharmacokinetics of perrimustine and cystemustine, 2 novel 2-chlor
oethylnitrosoureas (CENUs), were investigated in patients with various
cancer diseases. The unique protocol followed in this study consisted
of a 15-minute intravenous (IV) perfusion of a 45 mg/m2 dose of perri
mustine every 4 weeks and a 60 or 90 Mg/M2 dose of cystemustine every
2 weeks. A sensitive and specific method was developed using solid pha
se extraction and HPLC analysis, which allowed measurement of the drug
concentration levels until at least 3 hours after the beginning of ad
ministration of the injection. The rate of disappearance of the 2 drug
s from the blood was fitted to either a monoexponential or a biexponen
tial model. When detected, the half-lives of the distribution phase we
re less than 10 minutes. Regardless of the pharmacokinetic model used,
the elimination half-lives were about 50 minutes. The interindividual
variations of the pharmacokinetic parameters, as reflected by the var
iation coefficients (10 to 47%), were lower than those reported in the
literature for this class of unstable anticancer drugs. The procedure
described here allows one to safely conduct perrimustine and cystemus
tine pharmacokinetic studies with the purpose of further investigation
in a greater number of patients to determine whether any correlation
exists between pharmacokinetics, efficacy and/or toxicity.