Journal
JOURNAL OF NEURO-ONCOLOGY
Volume 61, Issue 3, Pages 203-207Publisher
KLUWER ACADEMIC PUBL
DOI: 10.1023/A:1022592913323
Keywords
temozolomide; pharmacokinetics; cerebrospinal fluid; blood-brain barrier; brain tumors
Categories
Ask authors/readers for more resources
Temozolomide is a prodrug that undergoes spontaneous chemical degradation at physiologic pH to form the highly reactive alkylating agent, methyl-triazenyl imidazole carboxamide ( MTIC). In clinical trials, temozolomide has activity in gliomas and is approved for recurrent anaplastic astrocytoma. We, therefore, studied the penetration of temozolomide into the cerebrospinal fluid (CSF) as a surrogate for blood-brain barrier penetration in a non-human primate model. Three Rhesus monkeys with indwelling Ommaya reservoirs received 7.5 mg/kg (150 mg/m(2)) of temozolomide as a 1 h intravenous infusion. Frequent blood and CSF samples were obtained over 24 h, plasma was immediately separated by centrifugation at 4degreesC, and plasma and CSF samples were acidified with HCl. Temozolomide concentration in plasma and CSF was measured by reverse-phase high-pressure liquid chromatography. Plasma temozolomide concentration peaked 0.5 h after the end of the infusion and was 104 +/- 3 muM. The mean peak CSF temozolomide concentration was 26 +/- 4 muM at 2.5 h. The mean areas under the temozolomide concentration-time curves in plasma and CSF were 392 +/- 18 and 126 +/- 18 muM h, respectively, and the CSF : plasma ratio was 0.33 +/- 0.06. Clearance of temozolomide was 0.116 +/- 0.004 l/kg/h, and the volume of distribution at steady state was 0.254 +/- 0.033 l/kg. In this non-human primate model, temozolomide penetrated readily across the blood-brain barrier. These findings are consistent with the activity of temozolomide in brain tumors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available