Effect of filgrastim on the pharmacokinetics of MX2 hydrochloride in patients with advanced malignant disease

Denis J. Morgan*, John S. Hill, Kerrie Clarke, Stan S. Stylli, Samantha J. Park, Jonathan Cebon, Russell L. Basser, Andrew H. Kaye, Howard Geldard, Darryl W. Maher, Michael D. Green

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Purpose: To investigate the effect of granulocyte colony-stimulating factor (G-CSF on the pharmacokinetics and pharmacodynamics of the new morpholino anthracycline drug MX2. Methods: A total of 25 patients with advanced malignant disease participated in a dose-escalation study in the first cycle of treatment given i.v. at doses of 50-80 mg/m2 (74-152 mg) with concomitant filgrastim CG-CSF, 5 μg/kg) given daily beginning at 24 h after the dose of MX2. Results: The mean fast distribution 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 values 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, respectively; P < 0.05). There was no correlation between plasma clearance and the delivered dose for the combined MX2-alone and MX2-filgrastim groups, indicating that the lower clearance observed in the G-CSF group was probably not due to the higher dose. Elimination half-lives of the metabolites 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 no relationship in the MX2-filgrastim group between the relative nadir neutrophil count and the dose or between the duration of grade IV neutropenia and the dose of MX2. Conclusions: This study shows that filgrastim decreased the plasma clearance of MX2 by approximately 25%, possibly by inhibition of metabolism.

Original languageEnglish
Pages (from-to)423-426
Number of pages4
JournalCancer Chemotherapy and Pharmacology
Issue number5
StatePublished - 1998
Externally publishedYes


  • Filgrastim G-CSF
  • MX2
  • Myelosuppression
  • Pharmacokinetics


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