Vaginal absorption

The absorption of drugs from the rectal [32] cavity has been studied in some detail. Muranishi et al. [34] have shown that a significant increase in the absorption and lymphatic uptake of soluble and colloidal macromolecules can be achieved by pretreating the rectal mucosal membrane with lipid-nonionic surfactant mixed micelles. They found no evidence of serious damage of the mucosal membrane. Davis [30] suggested that the vaginal cavity could be an effective delivery site for certain pharmaceuticals, such as calcitonin, used for the treatment of postmenopausal osteoporosis. 

Possible noninvasive routes for delivery of proteins include nasal, buccal, rectal, vaginal, transdermal, ocular, oral, and pulmonary. For each route of delivery there are two potential barriers to absorption permeability and enzymatic barriers. All of the... 

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-... 

Few, if any, products are administered via the vagina that are intended for systemic absorption. Thus, this route has not been as widely studied and characterized as others. On the other hand, large numbers of different products (douches, spermicides, antiyeast agents, etc.) have been developed that require introduction into the vagina in order to assert their localized effects. Increased research into different birth control and antiviral prophylaxis will result in more vaginal products in the future. All these must be assessed for vaginal irritation potential, and this serves as an example of the other tissue tolerance issues. 

Similarly, the 4-methoxy-2-naphthylamides of Leu, Ala, Arg, and Glu (6.1, R=side chain of amino acid, R =MeO) were used to assess the type and activity of aminopeptidase in homogenates of conjunctival, nasal, buccal, duodenal, ileal, rectal, and vaginal tissues from rabbits. This systematic comparison afforded a better understanding of the role of the aminopeptidase barrier in peptide absorption from oral vs. non-oral routes [18]. In a comparable manner, the y-glutamyltranspeptidase and dipeptidase activities were investigated in mammary tissue with the 4-nitroanilides of Leu, Met, Lys, Glu, and Asp (6.2, R=side chain of amino acid) [19]. 

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 surfaee area available for absorption in the buccal mucosa is much smaller than that in the GI, nasal, reetal, or vaginal mucosae. The bueeal mucosa is continuously bathed by saliva whieh reduees the drug concentration at the absorbing membrane. These two faetors, along with the permeability coefficient of the drug, affeet the overall absorption rate of a drug by this route. In addition, the bueeal mueosa is less permeable than any of the above mentioned mucosae. 

Vaginal Local or systemic effects (hormones) No first-pass metabolism Inconvenient Erratic absorption Irritation Creams, ointments, foams, tablets, pessaries... 

Miconazole (Monistat) is a broad-spectrum imidazole antifungal agent used in the topical treatment of cutaneous dermatophyte infections and mucous membrane Candida infections, such as vaginitis. Minimal absorption occurs from skin or mucous membrane surfaces. Local irritation to skin and mucous membranes can occur with topical use headaches, urticaria, and abdominal cramping have been reported with treatment for vagiiutis. 

Pharmacokinetics Oral. Maximum serum concentrations attained within 3 hours. Protein binding-. 96%-99%. Metabolized in liver. Excreted in bile and urine. Half-life 18.3 hr. IM Rapidly absorbed. Undergoes rapid metabolism. Half-life Few min. Long-acting form Approximately 10 wk. Vaginal Gel Rate limited by absorption rather than by elimination. Protein binding-. 96%-99%. Undergoes both biliary and renal elimination. Half-life 5-20 hr. 

Pharmacokinetics Extent of systemic absorption after vaginal administration may be dependent on presence of a uterus 5%-8% in women who had a hysterectomy versus 12%-16% in nonhysterectomized women. 

Pharmacokinetics Negligible absorption from vaginal application. 

H. Suppositories Solid preparations which melt at body temperature delivering medication for at-site treatment or for absorption at that point (usually rectal, vaginal, or urethral). Excipients include cocoa butter, waxy fatty acids, and derivatives, polyethylene glycol, theobroma oil, as well as many ingredients found in G. 

Vorherr H, Vorherr UF, Mehta P, Ulrich JA, Messer RH. Vaginal absorption of povidone-iodine. JAMA 1980 244(23) 2628-9. 

Systemic iodine absorption can occur after intravaginal administration of povidone-iodine (11). There were increases in serum iodine, protein-bound iodine, and inorganic iodine, but not serum thyroxine, after a 2-minute vaginal administration of povidone-iodine in non-preg-nant women (12). 

Touitou, E., M. Donbrow, and E. Azaz. 1978. New hydrophilic vehicle enabling rectal and vaginal absorption of insulin, heparin, phenol red and gentamicin. J Pharm Pharmacol 30 662. 

For a vaginally administered drug to exert a local or systemic effect, it must possess at least some degree of solubility in vaginal fluid. It is therefore important to consider the nature of vaginal fluid and, in particular, the characteristics of vaginal fluid that may effect vaginal absorption. 

The sequence of events leading to the absorption of a vaginally administered substance depends, in part, on the nature of the delivery system that is employed, i.e., whether it is solid or semisolid, swellable or erodible, soluble or insoluble, immediate or controlled release. 

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