Dj. Morgan et al., EFFECT OF FILGRASTIM ON THE PHARMACOKINETICS OF MX2 HYDROCHLORIDE IN PATIENTS WITH ADVANCED MALIGNANT DISEASE, Cancer chemotherapy and pharmacology, 41(5), 1998, pp. 423-426
Purpose: To investigate the effect of granulocyte colony-stimulating f
actor (G-CSF) on the pharmacokinetics and pharmacodynamics of the new
morpholino anthracycline drug MX2. Methods: A total of 25 patients wit
h advanced malignant disease participated in a dose-escalation study i
n the first cycle of treatment given i.v. at doses of 50-80 mg/m(2) (7
4-152 mg) with concomitant filgrastim (G-CSF, 5 mu g/kg) given daily b
eginning at 24 h after the dose of MX2. Results: The mean fast distrib
ution half-life (1.5 +/- 1.0 min) and the mean plasma clearance (2.18
+/- 0.95 l/min) were significantly lower than the respective mean valu
es found in a previous study in which 27 patients had received MX2 (16
.8-107.5 mg) alone (3.3 +/- 2.2 min and 2.98 +/- 1.68 l/min, respectiv
ely; P < 0.05). There was no correlation between plasma clearance and
the delivered dose for the combined MX2-alone and MX2-filgrastim group
s, indicating that the lower clearance observed in the G-CSF group was
probably not due to the higher dose. Elimination half-lives of the me
tabolites M1 and M4 were significantly greater in the filgrastim group
(19.8 +/- 14.7 and 11.8 +/- 5.0 h for M1 and 14.8 +/- 4.1 and 12.3 +/
- 6.3 h for M2, respectively). Unlike the MX2-alone group, there was n
o relationship in the MX2-filgrastim group between the relative nadir
neutrophil count and the dose or between the duration of grade IV neut
ropenia and the dose of MX2. Conclusions: This study shows that filgra
stim decreased the plasma clearance of MX2 by approximately 25%, possi
bly by inhibition of metabolism.