Rabbits vaginal

Dhondt, M.M.M., et al. 2005. The evaluation of the local tolerance of vaginal formulations containing dapivirine using the slug mucosal irritation test and the rabbit vaginal irritation test. Eur J Pharm Biopharm 60 419. 

Irritation test and the rabbit vaginal irritation test, Eur. I Pharrn. Biopharm., 60, 419-425. 

Salts of acetarsone are used in the treatment of intestinal amoebiasis, vaginal trichomoniasis, and necrotizing ulcerative gingivitis (Vincent s angina). The diethylamine salt (acetylarsan [534-33-8]) has antisyphilitic properties. Because of toxicity problems, safer dmgs have been developed. Oral LD q in rabbits is 150 mg /kg. 

Blaszcak DL Five day vaginal irritation pilot study in rabbits with rifaximin. East Milstone, Bio-Dynamics, 1991. 

The design of vaginal, rectal, and nasal irritation studies is less formalized, but follows the same basic pattern as the primary dermal irritation test. The rabbit is the preferred species for vaginal and rectal irritation studies, but the monkey and dog have also been used for these (Eckstein et al., 1969). Both the rabbit and rat have commonly seen use for nasal irritation evaluations. Defined quantities (typically 1.0 ml) of test solutions or suspensions are instilled into the orifice in question. For the vagina or rectum inert bungs are usually installed immediately thereafter to continue exposure for a defined period of time (usually the same period of hours as future human exposure). The orifice is then flushed clean, and 24 h after exposure it is examined and evaluated (graded) for irritation using the scale in Table 11.1. 

Acute Primary Vaginal Irritation Study in the Female Rabbit... 

Postmortem Procedures. Rabbits are euthanized by lethal dose of a barbiturate soon after the last vaginal irritation scores are collected. The vagina is opened by longitudinal section and examined for evidence of mucosal damage such as erosion, localized hemorrhage, and so on. No other tissues are examined. No tissues are collected. After the macroscopic description of the vagina is recorded, the animal is discarded. 

Overview of Study Design. Four groups of five adult rabbits each receive a single vaginal exposure daily for 10 days. The genitalia are examined daily. Animals are then euthanized and the vagina is examined macroscopically and microscopically. 

This study is very similar in design to that described previously for rabbits, with the following (sometimes obvious) exceptions. Mature ovariectomized female rats can be obtained from a commercial breeder. A 15% surplus should be obtained. Ten animals per group should be used (40 total for the study). The vaginal catheter is placed to a depth of approximately 2.5 cm and the treatment volume should be 0.2 ml. 

Eckstein, P., Jackson, M., Millman, N. and Sobero, A. (1969). Comparison of vaginal tolerance test of spermical preparations in rabbits and monkeys. J. Reprod. Fertil. 20, 85-93. 

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. 

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 day of identification of a vaginal plug or sperm in vaginal smear (rodents) or the day of observed or performed insemination (rabbits) is termed GDO. 

Ho, N.F.H., et al. 1976. Systems approach to vaginal delivery of drugs III Simulation studies interfacing steroid release from silicone matrix and vaginal absorption in rabbits. J Pharm Sci 65 1576. 

Schroder, A. et al. 2000. Absorption of oxybutynin from vaginal inserts Drug blood levels and the response of the rabbit bladder. Urology 56 1063. 

FIGURE 22.6 Permeability and permselectivity of vaginal and buccal epithelia in the rabbit, (a) Flux of 6-carboxyfluoroscein, a hydrophilic molecule, by in vitro perfusion studies steady-state flux ( xg/cm2/h x 106), (b) resistance (fl cm2 x 10 2), (c) thickness (p,m x 10-2), and (d) ratio of potassium transport number to chloride transport number, which is calculated from electrical measurements, used as indicative of the epithelium selectivity for positively charged molecules. (Modified from Sayani, A.P. and Chien, Y.W., Crit. Rev. Ther. Drug Carrier Syst. 13, 85, 1996.)... 

Morimoto, K., et al. 1982. Effective vaginal absorption of insulin in diabetic rats and rabbits using polyacrylic acid aqueous gel bases. Int J Pharm 12 107. 

C. L. Joyce and L. J. D. Zaneveld. Vaginal contraceptive activity of hyuluronidsse and cyckroaiygenase (prostaglandin synthetase) inhibitors in (he rabbit. Fert. Ster. 44 426 (1985). 

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