Metabolite urinary monkey

If CBN is formed in vivo, the appearance of oxygenated CBN metabolites as excretion products would be expected and this has proven to be the cast. Quite independently, Ben-Zvi et al. (23) has identified CBN-7-oic as a sizable fraction of the urinary monkey metabolites of A1-THC. It is, of course, possible that this metabolite could arise by a route not involving... 

Green et al. (1986) compared the metabolism of amphetamine in isolated hepatocyte suspensions from rat, dog, squirrel, monkey, and human livers. The metabolite profile of hepatocytes from each species corresponded to the profile of urinary metabolites identified previously. These results indicate that species-specific differences in the metabolic activation of compounds seen in vivo can be reproduced in vitro by the utilization of primary hepatocyte cultures. 

Isolation and characterization of the urinary metabolites. J. Chromatogr., 76, 321-330 Albro, P.W, Hass, J.R., Peck, C.C., Odam, D.G, Corbett, J.T, Bailey, F.J., Blatt, H.E. Barrett, B.B. (1981) Identification of the metabolites of di-(2-ethylhexyl) phthalate in mine from the African green monkey. Drug Metab. Dispos., 9, 223-225 Albro, P.W., Corbett, J.T, Schroeder, J.L., Jordan, S. Matthews, H.B. (1982) Pharmacokinetics, interactions with macromolecules and species differences in metabohsm of DEHP. Environ. Health Perspect., 45, 19-25... 

A half-life of 6 min for metabolism of di(2-ethylhexyl) adipate has been determined in rat small intestinal mucous membrane homogenates. The dominant urinary metabolite of di(2-ethylhexyl) adipate (500 mg/kg bw) in male Wistar rats is adipic acid, which accoimts for 20-30% of the administered oral dose. The other major metabolite which was found only in the stomach is mono(2-ethylhexyl) adipate (Takahashi et al., 1981). In cynomolgus monkeys, the glucuronide of mono(2-ethyl-hexyl) adipate and traces of unchanged di(2-ethylhexyl) adipate were foimd in the urine (BUA, 1996). 

In rats receiving a single oral dose of bis(2-chloro-l-methylethyl)ether of 0.0002-300 mg/kg bw, peak blood levels of radioactivity were reached at about 2-4 h. Following administration of a dose of 30 mg/kg bw, elimination was biphasic in rhesus monkeys, with half-lives of 5 h and two days, and monophasic in rats, with a half-life of two days. In rats, total recovery of radioactivity was 75% of an oral dose of the l- C-labelled compound and 90% after an intraperitoneal dose with the 2-i<-labelled compound approximately 20% of the oral dose was exhaled as CO2 in 48 h. Also in rats, urinary excretion of radioactivity accounted for 48% of a 90 mg/kg bw oral dose of the 1- relabelled compound within 48 h and for 60% of a 30 mg/kg bw intraperitoneal dose of the 2- rC-labelled compound within 24 h. Urinary metabolites identified after administration of an oral dose of 90 mg/kg bw of the I - ( -kibcllcd compound to rats were 2-(2-chloro-1-methylethoxy)propanoic acid (17% of the dose) and N-acetyl-5 -(2-hydroxypropyl)-cysteine (approximately 9% of the dose) following an intraperitoneal dose of the 2- 4C-labelled compound, metabolites identified were l-chloropropan-2-ol, propylene oxide and 2-(2-chloro-l-methylethoxy)propanoic acid (lARC, 1986). 

Vrbanac, J. J., O Leary, I. A., and Baczynskyj, L. (1992). Utility of the parent-neutral loss scan screening technique Partial characterization of urinary metabolites of U-78875 in monkey urine. Biol. Mass Spectrom. 21 517-522. 

A rhesus monkey study is also included (66) which species shows the trans-alcohol metabolite excreted as well. Urinary excretion consists of unchanged pentazocine and metabolites plus phenolic glucu-ronides of each. Fecal excretion consists of less than 1% administered dose (86). 

Gordon WP, Cheng H, Larsen DL, Ragner JA, Landmesser NG (1992) identification of urinary metabolites of 8-methyl-8-azabicyclo-[3,2,l] octan-3-yl 3,5-dichlorobenzoate (MDL 72,222) in the dog and monkey. Drug Metab Dispos 20 596-602... 

After intravenous administration, 46-63 per cent of radioactive indomethacin is rapidly excreted in the bile of dogs, guinea-pigs and monkeys. Radioactive material in the bile is largely reabsorbed in the intestine of the guinea-pig and monkey, but not of the dog . Renal clearance of the compound and its metabolites is the important excretory route in most species, except in the dog in which faecal excretion is high and urinary clearance negligible . 

The recovery values of radioactive doses in urine, bile, and feces of rats, monkeys, and humans administered [ C]muraglitazar are shown in Table 18.3 as an example. Urinary excretion of radioactivity was low (1.0, 0.5, 3.7, and 2.6% of dose for intact rats, dogs, monkeys, and humans, respectively) and the primary route of excretion was feces (87.7, 89.0, 80.4, and 61.6% of dose for intact rats, dogs, monkeys, and humans, respectively). The bile contained the majority of radioactivity from rats, mice, monkeys, and humans, representing the major elimination pathway of [ C]muraglitazar in these four species (Table 18.3). Table 18.4 shows the total concentrations of muraglitazar and its metabolites excreted in urine and bile in rats, dogs, monkeys, and humans. 

Only trace amounts of the unchanged drug was found in urine and bile. The major urinary metabolites are as follows a-hydroxy (l6), a-keto (1 ), p-hydroxy ( ), and a, P-dihydroxy ) derivatives of AA-jkk in rats 16 and salicylic acid derivative (2 ) in guinea pigs l6, 18 and a glucuronide (20) in rabbits 16 and 20 in dogs and 16 and 1 in monkeys (fable VI). ... 

In the metabolism study (29, 30, 31) the following seven metabolites, 6-(1-hydroxyethyl)-3-(Ijl-tetrazol-5-yl)-chromone (1 ), 6-acetyl-3-(lH-tetrazol-5-yl)chromone (I7)j 6-(2-hydroxyethyl)-3-(lH-tetrazol-5-yl)chromone (l ), (l,2-dihydroxyethyl)-3-( Ifl-tet razo 1 -5-y 1) chromone (1 ), glucuronide (20) (the structural elucidation is described below), 5 ethylsalicylic acid ( ) and 3-carboxy-4-hydroxy-phenylacetic acid ( ), were identified in the urine of rats, guinea pigs, rabbits, dogs and monkeys. These seven compounds were synthesized and used as reference compounds to unequivocally establish the structures of the urinary metabolites, and to allow evaluation of their antiallergic activity (32). The synthetic routes are shown below (Figure 4). 

Before being excreted into urine, TXB2 is degraded mainly by 8-oxidation. The major urinary metabolite was identified as dinor-TXB in the guinea pig, monkey and man, [188-192,194,195] in the rat, however, the major product was tetranor-TXB2 [193]. In the simian and human species, a number of additional metabolites were identified [190,195], which have been formed by various combinations of well-known metabolic reactions such as jS-oxidation and w-oxidation. Several metabolites, however, had the saturated keto structure in the side chain, and it was proposed that some of the break-down products were better substrates for the 15-hydroxy dehydrogenase than TXBj itself, or alternatively, that any formed... 

The metabolism of chloroform (CHCI3) has recently been reviewed (66, 131, 132). Studies in vivo have shown that CHClg administered orally to mice, rats, and monkeys is largely eliminated in expired air. Most of the administered dose was excreted unchanged in the monkey, whereas in the mouse C02 was the major metabolite in expired air. Metabolism of chloroform has been found to occur primarily in liver cells (77, 408, 473). Among the urinary metabolites obtained with KUlCls, [ Clurea has been identified (53). 

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