Lack of stereoselectivity in the pharmacokinetics and metabolism of the radiosensitizer Ro 03-8799 in man

During a clinical toxicity study it was possible to obtain urine samples from six patients receiving either the R-(-)- or S-(+)-stereoenantiomeric forms of the developmental 2-nitroimidazole radiosensitizer Ro 03-8799 (pimonidazole). Paired plasma samples were also obtained from four patients. The p...

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Bibliographic Details
Published in:Cancer chemotherapy and pharmacology 1991-01, Vol.28 (2), p.118-122
Main Authors: VORKMAN, P, NEWMAN, H. F. V, BLEEHEN, N. M, WARD, R, SMITHENC. E
Format: Article
Language:English
Subjects:
Adenocarcinoma - metabolism
Aged
Biological and medical sciences
Carcinoma, Squamous Cell - metabolism
Female
Humans
Lung Neoplasms - metabolism
Male
Medical sciences
Middle Aged
Nitroimidazoles - blood
Nitroimidazoles - metabolism
Nitroimidazoles - pharmacokinetics
Nitroimidazoles - urine
Radiation therapy and radiosensitizing agent
Radiation-Sensitizing Agents - metabolism
Radiation-Sensitizing Agents - pharmacokinetics
Stereoisomerism
Treatment with physical agents
Treatment. General aspects
Tumors
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Summary:During a clinical toxicity study it was possible to obtain urine samples from six patients receiving either the R-(-)- or S-(+)-stereoenantiomeric forms of the developmental 2-nitroimidazole radiosensitizer Ro 03-8799 (pimonidazole). Paired plasma samples were also obtained from four patients. The pharmacokinetic data were compared with those for the racemic mixture in the same individuals. The results revealed no major differences in the plasma pharmacokinetics, urinary clearance or N-oxidation of the individual enantiomers as compared with the racemic mixture. A similar lack of stereoselectivity with respect to the acute dose-limiting CNS toxicity syndrome suggests that this may not involve a specific CNS receptor interaction.
ISSN:0344-5704
1432-0843
DOI:10.1007/BF00689700