Abstract | PURPOSE: EXPERIMENTAL DESIGN:
Imatinib, 15 mg/kg i.v. over 30 min (n = 3) or 30 mg/kg p.o. (n = 3), was administered to nonhuman primates. Imatinib was measured in serial samples of plasma and CSF using high-pressure liquid chromatography with UV absorbance or mass spectroscopic detection. Pharmacokinetic parameters were estimated using model-independent methods. RESULTS: Peak plasma imatinib concentrations ranged from 6.4 to 9.5 microM after i.v. dosing and 0.8 to 2.8 microM after p.o. dosing. The mean +/-SD area under the plasma concentration versus time curve was 2480 +/-1340 microM.min and 1191 +/-146 microM.min after i.v. and p.o. dosing, respectively. The terminal half-life was 529 +/-167 min after i.v. dosing and 266 +/-88 min after p.o. dosing. After i.v. dosing the steady state volume of distribution was 5.9 +/-2.8 liter/kg, and the total body clearance was 12 +/-5 ml/min/kg. The mean peak CSF concentration was 0.25 +/-0.07 microM after i.v. dosing and 0.07 +/-0.04 microM after p.o. dosing. The mean CSF:plasma area under the plasma concentration versus time curve ratio for all of the animals was 5% +/-2%. CONCLUSIONS: There is limited penetration of imatinib into the CSF of nonhuman primates after i.v. and p.o. administration.
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Authors | Kathleen Neville, Robert A Parise, Patrick Thompson, Alexander Aleksic, Merrill J Egorin, Frank M Balis, Leticia McGuffey, Cynthia McCully, Stacey L Berg, Susan M Blaney |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 10
Issue 7
Pg. 2525-9
(Apr 01 2004)
ISSN: 1078-0432 [Print] United States |
PMID | 15073132
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antineoplastic Agents
- Benzamides
- Piperazines
- Pyrimidines
- Imatinib Mesylate
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Topics |
- Administration, Oral
- Animals
- Antineoplastic Agents
(blood, urine)
- Benzamides
- Chromatography, High Pressure Liquid
- Imatinib Mesylate
- Infusions, Intravenous
- Macaca mulatta
- Male
- Mass Spectrometry
- Piperazines
(blood, cerebrospinal fluid)
- Protein Binding
- Pyrimidines
(blood, cerebrospinal fluid)
- Time Factors
- Ultraviolet Rays
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