Vaginal and rectal routes of administration of test substances are not often used in animal testing procedures. However, these routes are almost obligatory when therapeutic agents intended for vaginal or rectal use in humans have to be evaluated for safety in animals. Applicable study designs and experiences with these routes are described in this report.
Aungst BJ, Lam G, Sheeter E. Oral and rectal nalbuphine bioavailability: first-pass metabolism in rats and dogs. Biopharm Drug Dispos1985;6:413–21.
2.
Behrendt WA, Cserepes J. Acute toxicity and analgesic action of a combination of buclizine, codeine and paracetamal ('Migraleve') in tablet and suppository form in rats. Pharmatherapeutics1985;4:322–31.
3.
Corbo DC, Liu J-C, Chien YW. Drug absorption through mucosal membranes: effect of mucosal route and penetrant hydrophilicity. Pharm Res1989;6:848–52.
4.
DeBoer AG, Van Hoogdalem EJ, Heijligers-Feijin CD, Verhoef J, Breimer PD. Rectal absorption enhancement of peptide drugs. J Controlled Release1990;241–6.
5.
DeMuynck C, Cuvelier C, Van Steenkiste D, Bonnarens L, Remon JP. Rectal mucosa damage in rabbits after subchronical application of suppository bases. Pharm Res1991;8:945–50.
6.
Draize JH. Dermal Toxicity, in: Appraisal of the safety of chemicals in foods, drugs and cosmetics. Washington, DC: The Association of Food and Drug Officials of the United States, 1959:46-59.
7.
Eckstein P, Jackson MCN, Millman N, Sobrero AJ. Comparison of vaginal tolerance tests of spermicidal preparations in rabbits and monkeys. J Reprod Fertil1969;20:85–93.
8.
Fix JA, Gardner CR. Rectal drug delivery: a viable alternative?Pharm Int1986;7:272–5.
9.
Food and Drug Administration, 21 CFR Part 351, Department of Health and Human Services, Part V. Vaginal contraceptive drug products for over-the-counter human use; establishment of a monograph; proposed rulemaking. Fed Register1990;45.
10.
Kaminsky M, Szivos MM, Brown KR, Willigan DA. Comparison of the sensitivity of the vaginal mucous membranes of the albino rabbit and laboratory rat to nonoxynol-9. Food Chem Toxicol1985;23:705–8.
11.
Kamiya A, Ogata H, Fung HL. Rectal absorption of nitroglycerin in the rat: avoidance of first pass metabolism as a function of rectal length exposure. J Pharm Sci1982;71:621–4.
12.
Katagiri Y, Itakura T, Naora K, Kanba Y, Iwamoto K. Enhanced bioavailability of morphine after rectal administration in rats. J Pharm Pharmacol1988;40:879–81.
13.
Lee VHL. Protease inhibitors and penetration enhancers as approaches to modify peptide absorption. J Controlled Release1990;13:213–23.
14.
Livingstone C, Livingstone D. Drug delivery. Part 4. Buccal and rectal routes. Pharm J1989;242:68–9.
15.
Morimoto K, Akasutchi H, Morisaka K, Kamada A. Effect of non-ionic surfactants in a polyacrylic gel base on the rectal absorption of [Asu1,7]-eel calcitonin in rats. J Pharm Pharmacol1985;37: 759–60.
16.
Okada H, Yamazaki I, Ogawa I, Hirai S, Yashiki T, Mima H. Vaginal absorption of a potent luteinizing hormone-releasing hormone analog (Leuprolide) in rats. I. Absorption by various routes and absorption enhancement. J Pharm Sci1982;71:1367–71.
17.
Pollock SR, Olanoff LS. Clinical pharmacology approaches to the assessment of novel drug delivery concepts. J Controlled Release1990;11:331–41.
18.
Staab RJ, Auletta CS, McConnell RF. Evaluation of toxicity of four superabsorbent laminates when exposed to the vaginal mucosa of rats, rabbits and sheep [abstract No. 1229]. Toxicologist1986;6.
19.
Staab RJ, Auletta CS, Blaszcak DL, McConnell RF. A relevant vaginal irritation/subacute toxicity model in the rabbit and ovariectomized rat [Abstract No. 1096]. Toxicologist1987;7.
20.
Van Hoogdalem EJ, Van Kan HJM, DeBoer AG, Breimer DD. Rate-controlled absorption enhancement of rectally administered cefoxitin in rats by salicylate. J Controlled Release1988;7:53–60.
21.
Van Hoogdalem EJ, Vermeig-Kerrs C, DeBoer AG, Breimer DD. Topical effects of absorption enhancing agents on the rectal mucosa of rats in vivo. J Pharm Sci1990;79:866–70.
22.
Zhou XH, Po A, Li W. Comparison of enzymatic activities of tissues lining portals of drug absorption, using the rat as a model. Int J Pharm1990;62:259–67.