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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 4/2010

Open Access 01-03-2010 | Original Article

Evaluation of the exposure equivalence of oral versus intravenous temozolomide

Authors: Blanca D. Diez, Paul Statkevich, Yali Zhu, Malaz A. Abutarif, Fengjuan Xuan, Bhavna Kantesaria, David Cutler, Marc Cantillon, Max Schwarz, Maria Guadalupe Pallotta, Fabio H. Ottaviano

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2010

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Abstract

Purpose

Oral temozolomide is approved in many countries for malignant glioma and for melanoma in some countries outside the USA. This study evaluated the exposure equivalence and safety of temozolomide by intravenous infusion and oral administration.

Methods

Subjects with primary central nervous system malignancies (excluding central nervous system lymphoma) received 200 mg/m2 of oral temozolomide on days 1, 2 and 5. On days 3 and 4, subjects received 150 mg/m2 temozolomide either as a 90-min intravenous infusion on one day or by oral administration on an alternate day.

Results

Ratio of log-transformed means (intravenous:oral) of area under the concentration–time curve and maximum concentration of drug after dosing for temozolomide and 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (MTIC) met exposure equivalence criteria (90% confidence interval = 0.8–1.25). Treatment-emergent adverse events were consistent with those reported previously in subjects with recurrent glioma treated with oral temozolomide, except for mostly mild and transient injection site reactions with intravenous administration.

Conclusions

This study demonstrated an exposure equivalence of a 90-min intravenous infusion of temozolomide and an equivalent oral dose.
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Metadata
Title
Evaluation of the exposure equivalence of oral versus intravenous temozolomide
Authors
Blanca D. Diez
Paul Statkevich
Yali Zhu
Malaz A. Abutarif
Fengjuan Xuan
Bhavna Kantesaria
David Cutler
Marc Cantillon
Max Schwarz
Maria Guadalupe Pallotta
Fabio H. Ottaviano
Publication date
01-03-2010
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 4/2010
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-009-1078-6

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