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Variations in schedules of ifosfamide administration: a better understanding of its implications on pharmacokinetics through a randomized cross-over study
- Source :
- Cancer Chemotherapy and Pharmacology. 60:375-381
- Publication Year :
- 2006
- Publisher :
- Springer Science and Business Media LLC, 2006.
-
Abstract
- The metabolism of ifosfamide is a delicate balance between a minor activation pathway (4-hydroxylation) and a mainly toxification pathway (N-dechloroethylation), and there remains uncertainty as to the optimal intravenous schedule.This study assesses ifosfamide pharmacokinetics (PK) according to two standard schedules. Using a 1:1 randomized trial design, we prospectively evaluated ifosfamide PK on two consecutive cycles of 3 g/m2/day for 3 days (9 g/m2/cycle) given in one of two schedules either by continuous infusion (CI) or short (3 h) infusion. Highly sensitive analytical methods allowed determination of concentrations of ifosfamide and the key metabolites 4-hydroxy-ifosfamide, 2- and 3-dechloroethyl-ifosfamide.Extensive PK analysis was available in 12 patients and showed equivalence between both schedules (3 h versus CI) based on area under the curves (micromol/l x h) for ifosfamide, 4-hydroxy-ifosfamide, 2- and 3-dechloroethyl-ifosfamide (9,379 +/- 2,638 versus 8,307 +/- 1,995, 152 +/- 59 versus 161 +/- 77, 1,441 +/- 405 versus 1,388 +/- 393, and 2,808 +/- 508 versus 2,634 +/- 508, respectively, all P0.2). The classical auto-induction of metabolism over the 3 days of infusion was confirmed for both schedules.This study confirms similar PK for both active and toxic metabolites of ifosfamide in adult cancer patients when 9 g/m2 of ifosfamide is administered over 3 days by CI or daily 3-h infusions.
- Subjects :
- Adult
Male
Cancer Research
Randomization
Continuous infusion
Pharmacology
Hydroxylation
Toxicology
Drug Administration Schedule
law.invention
chemistry.chemical_compound
Randomized controlled trial
Pharmacokinetics
law
Neoplasms
medicine
Humans
Pharmacology (medical)
Ifosfamide
Neoplasm Metastasis
Antineoplastic Agents, Alkylating
Cross-Over Studies
business.industry
Middle Aged
Crossover study
Nitrogen mustard
Oncology
chemistry
Area Under Curve
Pharmacodynamics
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 14320843 and 03445704
- Volume :
- 60
- Database :
- OpenAIRE
- Journal :
- Cancer Chemotherapy and Pharmacology
- Accession number :
- edsair.doi.dedup.....ae35f18dd3cbc1bc5b22e50efa96eedf