Dog Model

Lichtman et al. 2001 Tzavaraet al. 2000). A dog model of precipitated cannabinoid withdrawal, which includes increased salivation, vomiting, diarrhea, restless behavior, and trembling, has also been described (Lichtman et al. 1998). 

Watanabe M, Shin oka T, Tohyama S, et al. Tissue-engineered vascular autograft Inferior vena cava replacement in a dog model. Tissue Eng, 2001, 7, 429 39. 

Predictions of human in vivo permeability can be made with a particularly high degree of accuracy in all predinical models for drugs with passive diffusion as their main mechanism. It is only the dog model that seems to absorb low-permeability... 

The hypothesis that HNO is not involved during NO-release from sydnonimines was confirmed by the study of NO-release from C78-0652 109, the dimethyl derivative of SIN-1A (Scheme 6.19). This product closely resembles SIN-1A in its biological and pharmacological behavior, showing a clear NO-dependent vasodilating effect on guinea pig pulmonary arteries and hypotensive action in anesthetized and conscious dog models [105]. 

Pirsidomine showed a prolonged vasodilating activity in vitro and a long duration of action in vivo in a dog model. Compared with isosorbite-5-mononitrate (IS-5-MN) this sydnonimine developed no tolerance in a conscious dog model at doses of both drugs that produced similar pharmacological effects (Fig. 6.7) [121-123]. 

The lack of tolerance has been explained by the fact that the N O-release from these compounds is spontaneous and independent of the presence of thiols [124], that, by contrast, may be an essential cofactor in the action of the nitrate. Martorana et al. [125] showed a marked antiischemic effect of Pirsidomine in a dog model of myocardial infarction. 

In other work, C87-3754has been compared with SIN-1, the equivalent metabolite from molsidomine, and from the organic nitrate class, isosorbide-5-mononitrate (IS-5-MN) [146]. In this latter study, which involved long term oral administration in a dog model, IS-5-MN showed tolerance whilst the sydnonimines showed no self- or cross-tolerance. Elsewhere, tolerance studies in dogs by oral or continuous infusion of C87-3754 have shown benefits in the treatment of a failing heart, without tolerance [147] and with better results than those observed by nitroglycerin [148]. 

Desfluorositagliptin was clean in a 2-week exploratory safety study in rats and in an acute dog tolerability study, as described above. This compound did show some effects in the anesthetized, vagotomized cardiovascular (CV) dog model... 

The AEGL-2 was based on the threshold for cardiac sensitization using the dog model. Because this test is highly sensitive as the response to exogenous epinephrine is optimized, the 40,000 ppm concentration was adjusted by a single intraspecies UF of 3 to protect potentially susceptible individuals. An interspecies UF was not applied, because the dog is a reliable model for humans, and this is a highly sensitive test. Blood concentrations rapidly reach equilibrium, and the blood concentration determines the effect, so the 13,000 ppm value was used across all time periods. 

No information on potentially susceptible populations was located for HCFC-141b. A structurally related chemical, 1,1,1,2-tetrafluoroethane, has been tested in metered-dose inhalers for the treatment of asthma. Test subjects included adult and pediatric asthma patients as well as individuals with severe COPD. No adverse effects were reported (Smith et al. 1994 Taggart et al. 1994 Ventresca 1995 Woodcock 1995). The structurally related chemicals trichlorofluoromethane (CFC-11) and dichlorodifluoromethane (CFC-12) are presently used in metered-dose inhalers for the treatment of asthma but are phased out under the Montreal Protocol of 1987 (Alexander 1995). Structurally related compounds including 1,1,1-trichloroethane and trichlorofluoromethane were also tested for cardiac sensitization in a dog model with experimentally induced myocardial infarction. In these experiments cardiac sensitization occurred under the same conditions as in healthy dogs (Trochimowicz et al. 1976). 

Ideal for studying the dose-response relationship for QT interval prolongation taking into account all the pharmacological properties of a compound The dog model is one of the most widely used anesthetized rabbits (especially female rabbits) have also been proposed for high sensitivity It provides complementary information with respect to in vitro tests (activity of metabolites, measurement of plasma drug concentrations, calculation of the volume of distribution) Possibility to induce experimental TdP... 

The best statistical parameters were obtained by correlating the in vivo selectivity with the Vdif descriptor defined with respect to the oqa-AR supermolecule. It is worth noting that the oqa is the adrenergic receptor subtype of functional relevance for the urethra tissue (dog model) [8]. Thus, ligands showing high potency and selectivity for the lower urinary tract are those, which better fit the volume of the supermolecule that represents the binding site of the ala-AR subtype. 

Zhang J, Niu S, McJames S, Stanley T (1991a) Buccal absorption of insulin in an in vivo dog model—evidence of mucosal storage. Pharm Res 8 S—155... 

Zhang J, Niu S, Maland LJ, Barrus BK, Freimann VR, Hague BI (1991b) Buccal permeability of oral transmucosal fentanyl citrate (OTFCTM) in a dog model. Pharm Res 8 S-155... 

Oral dosing in rat and dog models measuring potency, duration of action, and plasma levels for effect... 

In 1976 Martin proposed the theory that there are three subtypes of opioid receptor on the basis of behavioural studies using a chronic spinal dog model which revealed that the opioids morphine (mu) (1), ketazocine (kappa) (2) and A-allylnormetazocine (SKF 10047) (4) (sigma) had different effects on respiration, heart rate and locomotor activity [13]. Furthermore, these ligands were unable to replace each other to prevent withdrawal symptoms in dogs that had been chronically treated with one of the compounds. 

The success of Matsushita s method and the encouraging developments in our laborabory set the stage for a decade of independent research into what we see as the best technology for the development of a liver-assist device. In a sense, Matsushita s work confirmed the structure of the device and our work confirmed the chemistry of the surface. Matsushita continued his work without the benefit of our technology and has successfully demonstrated the use of his device in a dog model. In a 1999 report, an artificial liver was reported to be equal, and probably superior to the most successful hollow-fiber device. 

A group at the Department of Chemical Engineering at Kyushu University in Fukuoka, Japan, spent the last decade working on a polyurethane foam scaffold for hepatic cells.In 1999, the group reported their work using a dog model that, showed that the performance of this system was equal, or probably superior to that of Demetriou s system, and in addition, our system improved renal function. This opinion is based on the comparison of various blood chemistries in the two devices (hollow hber vs. polyurethane foam). Table 7.2 depicts the comparison. 

S. Shelukar, G Kwei, and D. Storey (2004). The role of biopharmaceutics in the development of a clinical nanoparticle formulation of MK-0869 a beagle dog model predicts improved bioavailability and diminished food effect on absorption in humlait). J. Pharm, 285 135-146. 

Jacob, J., Pharmacokinetics of bioadhesive, gastroretentive, controlled release tablets of itraconazole (Spherazole CR) in beagle dog model. Controlled Release Society 33rd Annual Meeting and Exposition, 2005. 

Much of the experimental work with empty stomach handling of small objects and small volumes of liquid was conducted in the 1980s using dog models because of the similarity in the... 

Khoo, S.M., et al. 2001. A conscious dog model for assessing the absorption, enterocyte-based metabolism, and intestinal lymphatic transport of halofantrine. J Pharm Sci 90 1599. 

Zhang, J., et al. 1994. An in-vivo dog model for studying recovery kinetics of the buccal mucosa permeation barrier after exposure to permeation enhancers Apparent evidence of effective enhancement without tissue damage. Int J Pharm 101 15. 

Gilligan BJ, Shults MC, Rhodes RK, Updike SJ. Evaluation of a subcutaneous glucose sensor out to 3 months in a dog model. Diabetes Care 1994, 17, 882-887. 

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