Administration routes vaginal

Estrogens are also subject to extensive first-pass effects (it has been shown that these first-pass effects occur predominantly in the intestinal wall, rather than in the liver) after oral administration. Again, vaginal administration of estradiol results in higher bioavailability than via the oral route (Figure 11 4(b)). 

Recently, several in vitro experiments substantiated the potential of the human vaginal mucosa as a good administration route relating to the degree of permeation when compared with other mucosal surfaces. In fact, the vagina can be more permeable to some commonly used model substances, such as water, 17[3-cstradiol (Figure 3), arecoline, arecaidine, and vasopressin, than colonic or small intestinal mucosa, or at least as permeable as when compared to human buccal mucosa [46,47],... 

The lack of activity after oral administration for most peptides and proteins resulted in the past besides parenteral application into the utilization of nonoral administration pathways, for example, nasal, buccal, rectal, vaginal, percutaneous, ocular, or pulmonary drug delivery [27]. Drug delivery via these administration routes, however, is also frequently accompanied by presystemic degradation processes. Bioavailability of numerous peptides and proteins is, for example, markedly reduced after subcutaneous or intramuscular administration compared to their intravenous administration. The pharma-cokinetically derived apparent absorption rate constant is thus the combination of absorption into the systemic circulation and presystemic degradation at the absorption... 

Sustained- and controlled-release devices for drug delivery in the vaginal and uterine areas are most often for the delivery of contraceptive steroid hormones. The advantages in administration by this route—prolonged release, minimal systemic side effects, and an increase in bioavailability—allow for less total drug than with an oral dose. First-pass metabolism that inactivates many steroid hormones can be avoided [183,184],... 

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-... 

Vaginal Administration. Though not a common one, some materials do have routine exposure by this route (spermicides, tampons, douches, and antibiotics, for example), and, therefore, must be evaluated for irritation and toxicity by this route. The older preferred models used rabbits and monkeys (Eckstein et al., 1969), but, more recently, a model that uses rats has been developed (Staab et al., 1987). McConnell (1973) clearly described the limitations, particularly of volume of test material, involved in such tests. 

Other routes of administration used less commonly in dog safety studies are subcutaneous, intramuscular, intraperitoneal, rectal, and vaginal. 

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. 

Suppositories are pharmaceutical dosage forms intended for administration of medicine via the rectum, vagina, or urethra that melt, soften, or dissolve in the body cavity. Rectal and vaginal suppositories are most common but urethral suppositories are sometimes used. Suppositories are indicated for administering drugs to infants and small children, severely debilitated patients, those who cannot take medications orally, and those for whom the parenteral route might be unsuitable. Suppositories are used to administer drugs for either systemic or local application. Local applications include the... 

Routes of administration are either enteral or parenteral. The former term denotes all routes pertaining to the alimentary canal. Therefore, sublingual, oral, and rectal are enteral routes of administration. All other routes, such as intravenous, intramuscular, subcutaneous, dermal, vaginal, and intraperitoneal, are parenteral routes. 

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. 

Due to the lack of activity after oral administration for most peptides and proteins, administration by injection or infusion - that is, by intravenous (IV), subcutaneous (SC), or intramuscular (IM) administration - is frequently the preferred route of delivery for these drug products. In addition, other non-oral administration pathways have been utilized, including nasal, buccal, rectal, vaginal, transder-mal, ocular, or pulmonary drug delivery. Some of these delivery pathways will be discussed in the following sections in the order of the increasing biopharmaceutic challenges to obtain adequate systemic exposure. 

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