Absorption from the vagina

The acidic environment of the ear skin surface (around pH 6), sometimes referred to as the acid mantle of the ear, is thought to he a defence against invading microorganisms. 

Proteins and peptides, particularly in the presence of absorption enhancers, can be successfully administered by this route, although surfactant-based enhancers are apparently not effective in the vagina. Vaginal enzymes, especially the proteases, are likely to present problems in the vaginal delivery of proteins and peptides. 

Hydrogel-based vaginal pessaries to deliver prostaglandin E2 (to assist in ripening of the cervix prior to labour) progesterone and bleomycin have been developed. 

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MillarA. 1916. Perchloride of mercury poisoning by absorption from the vagina. Br Med J 2 453-454. 

Miconazole readily penetrates the stratum comeum and persists there for >4 days after application. Less than 1% is absorbed into the blood. Systemic absorption from the vagina is <1.3%. Adverse effects from vaginal application include burning, itching, or irritation in -7% of recipients, and infrequently, pelvic cramps (0.2%), headache, hives, or skin rash. Irritation, burning, and maceration are rare after cutaneous application. Miconazole is considered safe for use during pregnancy. 

Information about intravaginal clotrimazole is very sparse, but it appears not to interact with gliclazide or glibenclamide, and probably not with any of the other oral anti diabetics, not least because its absorption from the vagina is very small. 

Daneshmend, T.K. 1986. Systemic absorption of miconazole from the vagina. J Antimicrob Chemother 18 507. 

Robinson, G. D. (1925), Absorption from the human vagina, BJOG, 32,496-504. 

Rosenzweig, M. Walzer, M. Absorption of protein from the vagina and uterine cervix. Am. J. Obstet. Gynecol. 1943, 45, 286-290. 

Concern that the absorption of mercury from the vagina may be harmful has led to the recommendation that phenylmercuric nitrate should not be used in intravaginal formulations. ... 

Absorption of clotrimazole is less than 0.5% after application to the intact skin from the vagina, it is 3 to 10%. Fnngicidal concentrations remain in the vagina for as long as 3 days after application of the drug. The small amount absorbed is metabolized in the liver and excreted in bile. In adults, an oral dose of 200 mg per day will give rise initially to plasma concentrations of 0.2 to 0.35 pg/mL, followed by a progressive decline. 

There is evidence that miconazole is a very potent inhibitor of the metabolism of S-warfarin by the cytochrome P450 isoenzyme CYP2C9, and that it also inhibits the metabolism ofR-warfarin to a lesser extent." Even low oral doses of miconazole (125 mg daily) markedly inhibit warfarin metabolism, so it is not surprising that prescription doses of miconazole oral gel (480 to 960 mg daily) interact, since this is swallowed after retaining in the mouth. Very unusually, absorption of miconazole from the vagina (see also comments below) and even exceptionally through the skin, can result in increased anticoagulant effects. 

The systemic absorption of these drugs had previously been considered only from the standpoint of toxicity. However, in addition to local delivery, there has recently been considerable interest in the possibility of vaginal delivery for the systemic delivery of drugs, via the mucous membranes of the vagina. 

The vagina is a possible site for the systemic administration of various drugs. However, the low and erratic bioavailability of biopharmaceuticals via this route necessitates the use of absorption enhancers. Until safe, non-toxic absorption enhancers can be found, the route is of limited potential. A further major limitation of this route is the lack of reproducibility resulting from cyclic changes in the reproductive system. Finally, no matter what degree of optimization can be achieved via this route, it can only ever benefit approximately 50% of the population ... 

The vagina offers a substantial area for drug absorption because numerous folds in the epithelium increase the total surface area. A rich vascular network surrounds the vagina whereas the vaginal epithelium is covered by a film of moisture consisting mainly of cervical mucus and fluid secreted from the vaginal wall. 

Except for drugs especially designed for local gastrointestinal (GI) effects (see Chapter 38), the sulfonamides are absorbed rapidly and well from the GI tract. Peak plasma levels are achieved in 2-6 hours, depending on the drug. Absorption from sites such as the vagina, respiratory tract, or abraded skin is unrehable, but sufficient drug may enter the body to cause toxic reactions in susceptible persons or to produce sensitization. 

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