Vaginal drug absorption

Yotsuyanagi, T., et al. 1975. Systems approach to vaginal delivery of drugs I Development of in situ vaginal drug absorption procedure. J Pharm Sci 64 71. 

Monkeys, in particular Rhesus macaque and squirrel monkey, have been considered as models for vaginal drug absorption because of the similarities between nonhuman primate and human anatomy. The vagina of rhesus macaques is characterized by connective tissue attachments, localization of steroid hormone receptors, duration, and cyclic changes in vaginal physiology similar to that of humans [119]. 

Owada, E., et al. 1977. Vaginal drug absorption in rhesus monkeys. I. Development of methodology. J Pharm Sci 66 216. 

To improve the absorption of peptides and proteins, the employment of different enzymatic inhibitors has been suggested. For example, some authors have demonstrated the usefulness of inhibitors of both exo- and endopeptidases to promote calcitonin absorption across rat vaginal mucosa [93]. A direct relationship was found between the effect of peptidase inhibitors of in vitro degradation constant of calcitonin in vaginal mucosa homogenates and in vivo promotion of drug absorption, indicated by the decrease in plasma calcium levels after calcitonin administration in rats. The peptidase inhibitors tested were pepstatin, bestatin, and leupeptin. 

Hwang, S., et al. 1977. System approach to vaginal drug delivery of drugs. II. In situ absorption of unbranched aliphatic alcohols. J Pharm Sci 65 1574. 

Drug properties which affect vaginal drug delivery are broadly the same as those affecting transepithelial absorption at any site and have been discussed extensively in Chapter 1 (Section 1.3.4). 

Parenteral delivery routes are those that do not give rise to drug absorption into the splanchnic circulation. Thus, they avoid the possibility of hepatic first-pass metabolism. It should be noted that some parenteral routes do not avoid other first-pass metabolism effects (e.g., pleural metabolism for some inhaled drugs). Some major parenteral drug delivery routes are intraarterial, intrathecal, intravenous, intramuscular, trans-dermal, intranasal, buccal, inhalation, intraperitoneal, vaginal, and rectal. 

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. 

If the absorption, distribution, and elimination of a drug molecule after its release from a vaginal drug... 

The vaginal absorption of drug following its release from vaginal drug delivery devices may alternatively be described by a simplifled one-compartment open model with first-order drug absorption (Fig. 

The cyclic variation in vaginal drug permeability observed in rhesus monkeys in association with the rhythmic pattern of the sexual cycle suggests that the vaginal absorption data generated in the rhesus monkeys may be more reflective of what will occur in humans. The rhesus monkey is, therefore, a good animal model for the research and development of intravaginal delivery devices. 

Recently, some effervescent systems have been prepared that act as penetration enhancers for drug absorption, not only in oral forms but also in some topical forms, such as skin or vaginal applications. In these cases the reaction takes place directly after administration, in the mouth due to saliva (4), upon the wounds due to blood serum (5), or when formulated in a suppository. The effervescence can be provoked by the moisture of the vaginal mucosa to treat vaginal infections or by simply adjusting the pH. 

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