Rabbits rectal

I have a somewhat jaundiced view of this rabbit rectal hyperthermia business. One is presumably able to tell whether a compound is a stimulant or a psychedelic drug by the profile of the temperature rise, and how potent it will be by the extent of the temperature rise. But the concept of pushing thermocouples into the rear ends of restrained rabbits somehow does not appeal to me. I would rather determine both of these parameters from human studies. 

FIGURE 8.6 Permeation profiles of morphine (a) and a-CyD (b) through rabbit rectal mucosa after applications of morphine hydrochloride and a-CyD in Ringer s solution (pH 7.4) at 37°C. Each point represents the mean SE of four experiments. p < 0.05, compared with MH alone. 

What happens if you extend the chain to a third carbon The parent system is called the phenyl-(n)-propylamine, and the parent chain structure, either as the primary amine or as its alpha-methyl counterpart, represents compounds that are inactive as stimulants. The DOM-analogues have been made and are, at least in the rabbit rectal hyperthermia assay, uninteresting. A commercially available fine chemical known as piperonylacetone has been offered as either of two materials. One, correctly called 3,4-methylenedioxyphenylacetone or 3,4-methylenedioxybenzyl methyl ketone, gives rise upon reductive amination to MDA (using ammonia) or MDMA (using methylamine). This is an aromatic compound with a three-carbon... 

Historically, the rabbit pyrogen test constituted the most widely used method. This entails parenteral administration of the product to a group of healthy rabbits, with subsequent monitoring of rabbit temperature using rectal probes. Increased rabbit temperature above a certain point suggests the presence of pyrogenic substances. The basic rabbit method, as outlined in the European Pharmacopoeia, entails initial administration of the product to three rabbits. The product is considered to have passed the test if the total (summed) increase of the temperature of all three animals is less than 1.15 °C. If the total increase recorded is greater than 2.65 °C then the product has failed. However, if the response observed falls between these two limits... 

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. 

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]. 

Sznitowska M. et al.. Bioavailability of diazepam from aqueous-organic solution, submicron emulsion and solid lipid nanoparticles after rectal administration in rabbits, Eur. J. Pharm. Biopharm., 52, 159, 2001. 

Watanabe, Y., et al. 1992. Absorption enhancement of polypeptide drugs by cyclodextrins. I. Enhanced rectal absorption of insulin from hollow-type suppositories containing insulin and cyclodextrins in rabbits. Chem Pharm Bull 40 3042. 

Utoguchi, N., et al. 1998. Nitric oxide donors enhance rectal absorption of macromolecules in rabbits. Pharm Res 15 870. 

Watanabe, Y., et al. 1998. Studies of drug delivery systems for a therapeutic agent used in osteoporosis. I. Pharmacodynamics (hypocalcemic effect) of elcatonin in rabbits following rectal administration of hollow-type suppositories containing elcatonin. Biol Pharm Bull 21 1187. 

Watanabe, Y., et al. 1986. Pharamaceutical evaluation of hollow type suppositories. IV. Improvement of bioavailability of propranolol in rabbits after rectal administration. J Pharmacobiodyn 9 526. 

CyDs are known to be able to solubilize lipophilic drugs as well as lipophilic absorption enhancers, leading to the improvement of the enhancer s efficiency. There are some reports on the use of CyDs as a candidate for a coenhancer. For example, Yanagi et al. [35] reported that CyDs may promote the potency of absorption enhancers in rectum of rabbits. Inclusion complex of decanoic acid (CIO), an absorption enhancer, with a-CyD was prepared as an additive of cefmetazole sodium suppository and rectally administered to rabbits. Plasma concentration and area under the curve (AUC) of cefmetazole sodium after rectal administration of a suppository containing ClO-a-CyD complex to rabbits increased more significantly than those with no additive. 

Kondo, T., T. Irie, and K. Uekama. 1996. Combination effects of a-cyclodextrin and xanthan gum on rectal absorption and metabolism of morphine from hollow-type suppositories in rabbits. Biol Pharm Bull 19 280. 

Yanagi, H., et al. 1991. Effect of inclusion complexation of decanoic acid with a-cyclodextrin on rectal absorption of cefmetazole sodium suppository in rabbits. Yakugaku Zasshi 111 65. 

Ichikawa, K., et al. 1980. Rectal absorption of insulin suppositories in rabbits. J Pharm Pharmacol 32 314. 

Hosny, E.A. 1999. Relative hypoglycemia of rectal insulin suppositories containing deoxycholic acid, sodium taurocholate, polycarbophil, and their combinations in diabetic rabbits. Drug Dev Ind... 

Yamamoto, A., et al. 1992. A mechanistic study on enhancement of rectal permeability to insulin in the albino rabbit. J Pharmacol Exp Ther 263 25. 

Murakami, T., et al. 1981. Studies on absorption promoters for rectal delivery preparations. I. Promoting efficacy of enamine derivatives of amino acids for the rectal absorption of (3-lactam antibiotics in rabbits. Chem Pharm Bull 29 1998. 

Kim, S., et al. 1983. Effect of enamine derivatives on the rectal absorption of insulin in dogs and rabbits. J Pharm Pharmacol 35 100. 

Miyake, M., et al. 1984. Rectal absorption of lysozyme and heparin in rabbits in the presence of non-surfactant adjuvants. Chem Pharm Bull 32 2020. 

Matsumoto, Y., et al. 1989. Rectal absorption enhancement of gentamicin in rabbits from hollow type suppositories by sodium salicylate or sodium caprylate. Drug Des Deliv 4 247. 

Wakatsuki, K., et al. 2005. Effects of irradiation combined with cw-diamminedichloroplatinum (CDDP) suppository in rabbit VX2 rectal tumors. World J Surg 29 388. 

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