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Pharmacokinetics of decitabine administered as a 3-h infusion to patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
- Source :
-
Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2008 Apr; Vol. 61 (5), pp. 759-66. Date of Electronic Publication: 2007 Jun 13. - Publication Year :
- 2008
-
Abstract
- Purpose: In this study, pharmacokinetics (PK) of decitabine administered as a 3-h intravenous infusion of 15 mg/m2 every 8 h for 3 days (cycles repeated every 6 weeks) was evaluated in patients with MDS or AML.<br />Methods: The PK of this dosing regimen was evaluated in sixteen patients with MDS or AML. Plasma samples were obtained pre-dose and during the first 8-h dosing interval on each dosing day during Cycle 1, and at pre-dose and just prior to the end of infusion during Cycle 2. PK samples were assayed for decitabine by a sensitive and specific validated liquid chromatography-tandem mass spectrometry method.<br />Results: The mean maximum observed plasma concentration (Cmax), 64.8-77.0 ng/ml, and the mean area under the plasma concentration-time curve (AUC0-infinity), 152-163 ng h/ml, were unchanged during dosing of decitabine for 3 days. The time to the maximum concentration (Tmax) generally occurred at the end of infusion. The mean values for terminal phase elimination half-life (0.62-0.78 h), total body clearance (125-132 l/h per m2), and volume of distribution at steady state (62.7-89.2 l/m2), remained unchanged during the every 8 h dosing (P>0.05). Cycles 1 and 2 Cmax values for days 1, 2, and 3 were not significantly different as determined by paired two-tailed t test (P>0.05). The primary toxicity of decitabine was myelosuppression, which was observed in all patients. Two deaths, from sepsis, were considered possibly related to decitabine.<br />Conclusions: Decitabine dosed at 15 mg/m2 iv every 8 h for 3 days resulted in a predictable and manageable toxicity profile in patients with MDS/AML. The repeated dosing did not result in systemic accumulation of the drug, and decitabine PK remained unchanged from cycle to cycle.
- Subjects :
- Adult
Aged
Aged, 80 and over
Antimetabolites, Antineoplastic adverse effects
Area Under Curve
Azacitidine adverse effects
Azacitidine pharmacokinetics
Bone Marrow drug effects
Bone Marrow pathology
Chromatography, High Pressure Liquid
Decitabine
Drug Administration Schedule
Female
Half-Life
Humans
Infusions, Intravenous
Male
Mass Spectrometry
Middle Aged
Sepsis etiology
Tissue Distribution
Antimetabolites, Antineoplastic pharmacokinetics
Azacitidine analogs & derivatives
Leukemia, Myeloid, Acute drug therapy
Myelodysplastic Syndromes drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0344-5704
- Volume :
- 61
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cancer chemotherapy and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 17564707
- Full Text :
- https://doi.org/10.1007/s00280-007-0531-7