Cervical tissue uptake of all-trans-retinoic acid delivered via a collagen sponge-cervical cap delivery device in patients with cervical dysplasia

The present study was undertaken to evaluate the systemic absorption and cervical tissue uptake of all-trans-retinoic acid (TRA), delivered via a collagen spongecervical cap delivery device in patients with intraepithelial cervical dysplasia. Ten patients with histologically proven mild or moderate...

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Bibliographic Details
Published in:Investigational new drugs 1986-01, Vol.4 (3), p.245-249
Main Authors: Peng, Y M, Alberts, D S, Graham, V, Surwit, E A, Weiner, S, Meyskens, Jr, F L
Format: Article
Language:English
Subjects:
Administration, Topical
Cervix Uteri - metabolism
Collagen
Dose-Response Relationship, Drug
Female
Humans
Tretinoin - administration & dosage
Tretinoin - metabolism
Tritium
Uterine Cervical Dysplasia - metabolism
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Summary:The present study was undertaken to evaluate the systemic absorption and cervical tissue uptake of all-trans-retinoic acid (TRA), delivered via a collagen spongecervical cap delivery device in patients with intraepithelial cervical dysplasia. Ten patients with histologically proven mild or moderate cervical dysplasia were included in this pharmacologic study. The two TRA concentrations (0.05% and 0.372%) selected for study represent the starting and maximally tolerated doses used in phase I clinical trial. All-trans-retinoic-11-3H acid (3H-TRA, 500 mu Ci) was used to facilitate cervical tissue uptake studies. Cervical biopsies and post-treatment blood samples were obtained from each patient after TRA exposure. The uptake of TRA into cervical tissues four hours after drug administration was significantly increased at the maximally tolerated TRA dose. There was a rapid decrease in cervical tissue concentration of TRA at the 0.372% dose between 4 and 24 h after drug exposure, suggesting a relatively short elimination half-life of TRA in cervical tissues. HPLC analysis of post-treatment blood samples indicate that there was no systemic absorption of TRA after local cervical administration.
ISSN:0167-6997
1573-0646
DOI:10.1007/BF00179591