Vaginal route

Penetration enhancers are low molecular weight compounds that can increase the absorption of poorly absorbed hydrophilic drugs such as peptides and proteins from the nasal, buccal, oral, rectal, and vaginal routes of administration [186], Chelators, bile salts, surfactants, and fatty acids are some examples of penetration enhancers that have been widely tested [186], The precise mechanisms by which these enhancers increase drug penetration are largely unknown. Bile salts, for instance, have been shown to increase the transport of lipophilic cholesterol [187] as well as the pore size of the epithelium [188], indicating enhancement in both transcellular and paracellular transport. Bile salts are known to break down mucus [189], form micelles [190], extract membrane proteins [191], and chelate ions [192], While breakdown of mucus, formation of micelles, and lipid extraction may have contributed predominantly to the bile salt-induced enhancement of transcellular transport, chelation of ions possibly accounts for their effect on the paracellular pathway. In addition to their lack of specificity in enhancing mem-... 

Nissen, E., Uvnas-Moberg, K., Svensson, K., Stock, S, Widstrom, A. M., and Winberg, J. 1996. Different patterns of oxytocin, prolactin but not cortisol release during breast feeding in women delivered by caesarean section or by the vaginal route. Early Human Development, in press. 

The vaginal route is eonsidered to be suitable for the loeal applieation and absorption of therapeuties like estrogens for hormone replaeement therapy or contraception. Systemic absorption of peptide drugs sueh as LHRH agonists and ealcitonin can also be achieved [65]. 

The rectal route/vaginal route (drug administered locally to give a systanic effect),... 

Antiprogestins (eg, mifepristone) have been combined with an oral oxytocic synthetic analog of PGE1 (misoprostol) to produce early abortion. This regimen is available in the USA and Europe (see Chapter 39). The ease of use and the effectiveness of the combination have aroused considerable opposition in some quarters. The major toxicities are cramping pain and diarrhea. The oral and vaginal routes of administration are equally effective, but the vaginal route has been associated with an increased incidence of sepsis, so the oral route is now recommended. 

Patients at low risk of developing osteoporosis who manifest only mild atrophic vaginitis can be treated with topical preparations. The vaginal route of application is also useful in the treatment of urinary tract symptoms in these patients. It is important to realize, however, that although locally administered estrogens escape the first-pass effect (so that some undesirable hepatic effects are reduced), they are almost completely absorbed into the circulation, and these preparations should be given cyclically. 

Richardson, J.L., and L. Ilium. 1992. Routes of delivery—Case studies. The vaginal route of peptide and protein drug delivery. Adv Drug Deliv Rev 8 341. 

Miles, R.A., et al. 1994. Pharmacokinetics and endometrial tissue levels of progesterone after administration by intramuscular and vaginal routes A comparative study. Fertil Steril 62 485. 

Strategies to Improve Systemic and Local Availability of Drugs Administered via Vaginal Route... 

In recent years, several studies demonstrated successful DNA immunization via the vaginal route [6]. Moreover, there is increasing evidence that prolonged induction of immunoglobulin IgA secretion provides protection against sexually transmitted pathogens and spermatozoa [108],... 

The use of vertebrates to evaluate tolerability and absorption of drug administered via the vaginal route has been widely criticized on the basis of scientific and ethical considerations. Studies on animals can be substituted by validated in vitro tests as described in the guideline issued by Committee for Proprietary Medicinal Products (CPMP), now Committee for Medicinal Products for Human Use (CHMP) [112], Before an in vitro test can be considered valid, this test must undergo a procedure aimed at establishing its relevance and reliability. The relevance of the alternative test has to be compared with accepted in vivo standard methods. 

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