Vaginal hydrolysis of retinyl acetate: increase in plasma retinol and retinol binding protein in women with cervical dysplasias.
We previously reported the clinical feasibility of a Phase I trial involving the topical administration of a RA gel applied cervicovaginally in women with mild or moderate cervical dysplasia. Now, we report hydrolysis and systemic absorption of the RA gel from the vagina. HPLC analysis of samples of residual gel obtained from the cervical canal after topical bolus application indicate that the RA undergoes prompt in vivo hydrolysis yielding retinol as a major metabolite. Venous blood samples of 41 subjects, who self-administered a RA gel, were analyzed for plasma retinol and RBP concentrations prior to and upon completion of a 7-day treatment course and upon return for follow-up examinations. An increase in both the concentrations of plasma retinol and RBP were detected after topical application of the RA gel. These elevated values receded after the gel administration was discontinued. No significant changes were observed in plasma retinol or RBP concentrations in placebo-treated subjects. The efficacy of RA as a chemopreventive agent in treating cervical dysplasias remains to be determined.
Palan
P R
PR
Department of Obstetrics and Gynecology, Albert Einstein College of Medicine, Bronx, New York 10461.
Basu
J
J
Romney
S L
SL
D004224:Diterpenes; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D012177:Retinol-Binding Proteins / Q000032:analysis*; D054839:Retinol-Binding Proteins, Plasma; D000084562:Retinyl Esters; D002578:Uterine Cervical Dysplasia / Q000188:drug therapy / Q000378:metabolism*; D014621:Vagina / Q000378:metabolism*; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use
D004224:Diterpenes; D012177:Retinol-Binding Proteins; D054839:Retinol-Binding Proteins, Plasma; D000084562:Retinyl Esters; D014801:Vitamin A; C009166:retinol acetate