Urination species differences

N,N-diallylmelamine , vasodilator. Rat, dog, man. Extensively metabolized. N-oxidation (triazine ring, reversible reaction) to form active metabolite, then deallylation and N-reduction (rat) direct deallylation (M) (all species) hydroxylation of allyl group N-methylation (triazine ring) then deallylation UP in urine. Species difference - man does not produce active metabolite, (N-hydroxy triazine derivative). 

Fenfluramine, anorexigen. Man, dog. Deethylation (m) deethylation and side chain oxidation, then gly. conj. (M) UP (m) and trlfluorome-thylhippuric acid (M) in urine. Dog, unlike man, free trifluoromethyl-benzolc acid in urine. Species difference. 

Pronethalol, adrenergic blocker . Metabolized.via 2 pathways (a), N-dealkylation follo /ed by oxidation, forming 2-naphthyl-glycollic acid (m) which is oxidatively decarboxylated (m) ( ), ring hydroxylation at C-7 and glue. UP (t) in urine. species difference in pathway. 

Intravenous administration of endosulfan (7 3 ratio of a- and P-isomers) in rabbits produced slower elimination of the a-isomer (Gupta and Ehrnebo 1979). Excretion of the two isomers occurred primarily via the urine (29%) with much less excreted via the feces (2%). Given the earlier evidence in rats and mice describing the principal route of elimination of endosulfan and its metabolite to be via the feces, the differences in the excretion pattern in this study may be attributable to differences in exposure routes, to species differences, or to both. Nevertheless, studies in laboratory animals suggest that both renal and hepatic excretory routes are important in eliminating endosulfan from the body. Elimination of small doses is essentially complete within a few days. 

Fig. 7.7 Discrimination by F. (a) of estrous, vs. non-estrous, urine frequency in feral goats (from O Brien, 1982) and (b) within social groups, species-differences in responsiveness of male antelopes to urinary and/or genital signals (from Hart and Hart, 1987).

Urinary excretion patterns of thiocyanate suggest that there are quantitative species differences in acrylonitrile metabolism (Ahmed and Patel 1981). Thiocyanate was identified as a metabolite in rats, mice, rabbits and Chinese hamsters. About 20 to 23% of the administered dose was excreted as thiocyanate in rats, rabbits and Chinese hamsters, while 35% was excreted as thiocyanate in mice (Gut et al. 1975). It has also been observed that mice metabolize acrylonitrile more rapidly than rats (Ahmed and Patel 1981 Gut et al. 1975). Maximum blood cyanide concentrations were observed 1 hour after dosing in mice, but 3 hours after dosing in rats (Ahmed and Patel 1981). In mice, thiocyanate was present in the urine within 4 hours of dosing, while in rats, thiocyanate was present in urine only at time intervals longer than 4 hours (Gut et al. 1975). 

The same diet affects species differently. For instance, mountain hares, Lepus timidus, consume much hirch in their winter diet, while European hares, Lepus europaeus, do not. A high concentration of hirch phenolics in the diet causes massive sodium loss via the urine in European hares, but not in mountain hares (lason and Palo, 1991). Further, among laboratory rodents, hamsters are extremely sensitive to tannins while rats and mice easily adjust within 3 days to doses of condensed tannins that are lethal to hamsters (Mehansho etal, 1987). 

Species differences in the metabolism of propachlor are summarized in Table II. All species studied metabolized propachlor in the MAP. Obvious, but unexplained differences are that the rat excreted no cysteine conjugate and the chicken formed no methylsulfonyl-containing metabolites. The absence of methylsulfonyl formation by chickens is thought due to the low biliary secretion of first pass metabolites. The ruminant (sheep) excreted large amounts of cysteine conjugate in urine which is also not explained. We do not know if the intestinal flora are involved in the formation of the methylsulfonyl acetanilides isolated from sheep urine. 

The kidney of most fish is primarily involved in hematopoiesis and osmoregulation. Fresh-water fish are hypertonic relative to the water. The continual osmotic uptake of water is balanced by production of as large amounts as 2-4 ml/kg/h of dilute urine. Salt-water fish, on the other hand, are hypotonic relative to their environment, resulting in body water loss. In response, marine species produce much smaller volumes of urine. Large differences exist among different fish species in regard to nephron structure to facilitate these functional responses. These features may influence the renal contribution to drug disposition apprecia-... 

A recent example of a species difference in metabolism causing a difference in toxicity is afforded by the alicyclic hydroxylation of the oral antiallergy drug, proxicromil (Fig. 5.11). After chronic administration, this compound was found to be hepatotoxic in dogs but not in rats. It was found that dogs did not significantly metabolize the compound by alicyclic oxidation, whereas rats, hamsters, rabbits, and man excreted substantial proportions of metabolites in the urine. In the dog, biliary excretion was the route of elimination of the unchanged compound,... 

Agurell (30) has observed species differences in excretion patterns as is illustrated in Figure 9. The rat resembles man in having a low proportion of metabolites in the urine the rabbit, on the other hand, disposes of most of the metabolites via the kidney. These differences are also reflected in the rate of excretion the rabbit being the most rapid. 

Occurrence and formation of TBC 30, the condensation product of serotonin with acetaldehyde, has received special attention by the Swedish group of Beck and colleagues. They found TBC 30 to be present in human urine and in animal tissues, in which it is often excreted in conjugated form (59). Analysis of tissue extracts using GC-MS techniques and chiral columns showed the compound to be present in rat brain and to be excreted in the urine of different animal species in unequal proportions of the enantiomers (60,61). Unequal proportions of deuterated TBC 30 enantiomers were found when rats were fed trideuterated ethanol (30). TBC 30 occurs in the urine of controls and alcoholics in comparable amounts and is excreted mostly in conjugated form (62). The methyl ether TBC 31 is a... 

NMR comparisons of biochemistry of urine from different species 43... 

J2, NMR comparisons of biodiemistry of urine from different species... 

Although hippuric acid was detected in urine of humans consuming both green and black tea, studies in rats indicated that these animals do not seem to produce hippuric acid from pure catechin, but a species difference between humans and rats cannot be excluded. ... 

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