Rhesus monkey urine

The most significant information in the present study arises from a radically different approach to these metabolite investigations. Four years ago, we reported that an appreciable proportion of the total radioactivity in Rhesus monkey urine could be extracted with ether, even without prior hydrolysis (13). This excretion was highly pH-dependent -- with the curve s inflection point being near pH 4 (Figure 12) — indicating that the materials being extracted were probably carboxylic acids. 

Following oral administration of 1 mg/kg 14C mirex to a female rhesus monkey, 25% of the 14C was recovered in the feces within 48 hours, with a cumulative excretion of 26.5% over 23 days. Less than 1% was recovered in the urine over 23 days (Wiener et al. 1976). A monohydro derivative of mirex was identified in the feces of rhesus monkeys given daily doses of 1 mg/kg mirex (Stein and Pittman 1977). The exact duration of dosing was not specified (Stein and Pittman 1977). 

Absorption of pentachlorophenol is relatively rapid in all species studied, but elimination differs between species and also between sexes. Metabolism occurs through glucuronic acid conjugation and hydrolytic dechlorination to tetrachlorohydroquinone, which is further conjugated. In contrast to rodents, rhesus monkeys eliminate pentachlorophenol in urine unchanged (lARC, 1991). 

Study of intermittent effluxes of acid phosphatase activity in the urine of mature human males 29) led to the discovery of the enzyme in semen and prostate by Kutscher and Wolberg (S). The enzyme is very active in human prostatic tissue and the caudal lobe of the rhesus monkey. Dog prostate contains much less enzyme than human tissue. Cat, guinea pig, rabbit, and rat prostates contain little (SO). Synthesis... 

The metabolism of the benzidine-based dyes C.I. Direct Red 28, C.I. Direct Blue 6, C.I. Direct Brown 95, and C.I. Direct Black 38 was studied in Rhesus monkeys. After ingestion of the dyes, benzidine and monoacetylbenzidine could be detected as metabolites in the urine. This indicated that the dyes had been converted to benzidine [29], Recent in vitro studies on C. I. DirectBlue 14 show that bacteria isolated from healthy human skin have reductase activity and are able to cleave the dye into the corresponding arylamine, in this case 3,3 -dimethylbenzi-dine [30],... 

Studies of pentazocine biological disposition in animals consist of tissue uptake (26,52,58,65, 68,79), blood level (50,61,7 0 and urine level determinations (88). While animal metabolic pathways identified (39. 0,70) are similar to those found in man, additional products have been demonstrated. In the rat 9-methoxypentazocine (or its 8-methoxy-9-hydroxy isomer), 8,9 (or 9.8)-methoxy-hydroxy metabolite of the cis-alcohol product and 8,9 (or 9,8)-methoxyhydroxy metabolite of the transalcohol product were found. Pharmacokinetic studies have been done in rhesus monkey (66) and in the dog (35t5 63) Typical plasma half-lives measured in dog plasma are 1.2-1.6 hours. A day-night variation was also observed in the calculated parameters (35). 

DEHP does not appear to be readily absorbed through the human skin. Wester et al. (1998) estimated that dermal absorption amounts to approximately 1.8% of a 24-hour applied dose of DEHP solubilized in ethanol. They noted that 1.1% of the radioactivity from a 24-hour dermal application of 14C-labeled DEHP to the forearm of volunteers was excreted in the urine within 7 days postapplication. They used this finding and the observation that approximately 60.8% of an intravenously-injected dose of DEHP was excreted in the urine of Rhesus monkeys over the same posttreatment time period as the basis for their estimate. No other reports were located regarding dermal absorption of DEHP in humans. 

Twenty-four hours after a single intravenous injection of 14C-DEHP to rats, the radioactivity was mainly recovered in the urine and feces, suggesting that the major excretory pathways in rats are the urine and bile (Schulz and Rubin 1973). Excretion was dose-dependent as shown by the fact that 50-60% of the injected radioactivity from a low dose was recovered in urine and feces, whereas less than 50% was recovered when a high dose was injected (Schulz and Rubin 1973). In Rhesus monkeys, 60.8% of the radioactivity in an intravenously injected dose of radiolabeled DEHP was excreted in the urine during 7 days postinjection, more than half of which was eliminated in the first day (Wester et al. 1998). 

Direct HPLC analysis of urine extracts appears feasible for A -THC. 215nm is the optimum wavelength for detection of THC-class compounds. Dual wavelength at 215 and 280nm serves as a valuable check on cannabinoid retention assignment and as a screen for unknown THC or CBN-class metabolites. The latter feature was demonstrated in the observance of CBN-class peaks in both hexane and E-I extracts. This observation suggests a CBN-metabolic route of A -THC. Evidence of a CBN-metabolic route for A -THC has been reported by McCallum (8) and Green (6) for humans and by Ben Zvi et al (9) for rhesus monkeys. 

In vivo experiments on 4 human volunteers, to whom 0.0026 mg/cm2 of 14C-benzene was applied to forearm skin, indicated that approximately 0.05% of the applied dose was absorbed (Franz 1984). Absorption was rapid, with more than 80% of the total excretion of the absorbed dose occurring in the first 8 hours after application. Calculations were based on urinary excretion data and no correction was made for the amount of benzene that evaporated from the applied site before absorption occurred. In addition, the percentage of absorbed dose excreted in urine that was used in the calculation was based only on data from rhesus monkeys and may not be accurate for humans. In another study, 35-43 cm2 of the forearm was exposed to approximately 0.06 g/cm2 of liquid benzene for 1.25-2 hours (Hanke et al. 1961). The absorption was estimated from the amount of phenol eliminated in the urine. The absorption rate of liquid benzene by the skin (under the conditions of complete saturation) was calculated to be low, approximately 0.4 mg/cm2/hour. The absorption due to vapors in the same experiment was negligible. The results indicate that dermal absorption of liquid benzene is of concern, while dermal absorption from vapor exposure may not be of concern because of the low concentration of benzene in vapor form at the point of contact with the skin. No signs of acute intoxication due to liquid benzene dermally absorbed were noted. These results confirm that benzene can be absorbed through skin. However, non-benzene-derived phenol in the urine was not accounted for. 

Soman Urine PMPA Detected in urine of rhesus monkeys GC-NPD, FPD, MS LC-MS Riches et al (2005)... 

Evans, and those associated with him, found that mannide mono-oleate was neither acutely nor chronically toxic in the diet of the white rat or in the diet of the Macacus rhesus monkey. The ester was shown to be absorbed from the intestinal tract of the rat. It was not re-excreted into the gut. Evidench of metabolism was produced by the isolation of crystals of isomannide from the urines of rats ingesting the compound. 

Female Sprague-Dawley rats were exposed dermally to H]-benzo[a]pyrene (1 ppm) containing petroleum crude oil alone or in fortified soil matrix for 4 days (Yang et al. 1989). Recovery of radioactivity was 35.3% of the dose applied in oil, as follows urine (5.3% of dose), feces (27.5%), and tissues (2.5%) 96 hours after beginning of exposure. Recovery was 9.2% of applied dose with benzo[a]pyrene from petroleum crude-fortified soil recoveries in urine, feces, and tissues were 1.9%, 5.8%, and 1.5%, res 3ectively, at 96 hours. Benzo[a]pyrene (10 ppm) with acetone vehicle or in soil was applied to a 12 cm area of abdominal skin of female rhesus monkeys for 24 hours (Wester et al. 1990). Urine contained 51 22% of the dose with acetone vehicle and 13.2 3.4% with soil. 

In a related study. Wester et al. (1990,1993) assessed the in vivo percutaneous absorption of PCBs in adult female Rhesus monkeys. " C-Labeled Aroclor 1242 and 1254 were separately administered iv and topically to Rhesus monkeys and urinary and fecal excretion of radioactivity was measured for the next 30 days. Following iv administration, the 30-day cumulative excretion was 55% of the administered dose (39% urine, 16% feces) for Aroclor 1242 and 27% (7% urine, 20% feces) for Aroclor 1254. The percentage of the dose absorbed following topical administration to abdominal skin (after light clipping of hair) was estimated from the ratio of the total urinary and fecal excretion following topical and iv administration. Topical administration of Aroclor 1242 in soil, mineral oil, tiichlorobenzene, or acetone resulted in 14, 20, 18, and 21% absorption of the administered dose, respectively. In contrast to the above in vitro results with human skin, the vehicle had little effect on the systemic absorption of the PCBs applied to the skin of monkeys. This may be due to the uncertain viability of the human skin used in the in vitro studies and the fact that the in vitro study primarily assessed retention of PCBs in human skin and could not estimate systemic absorption. 

Following intravenous injection of 32.7 pg Aroclor 1242 to Rhesus monkeys, 39.4% of the administered dose was excreted in the urine, and 16.1% was excreted in the feces over a 34-day period (Wester et al. 

A potentially important use of MTX diesters has been proposed to be in the treatment of tumours of the central nervous system [292]. Rosowsky et al. [309] examined the pharmacokinetics and metabolism of DBMTX in Rhesus monkeys, and demonstrated that when only free (i.c., not protein-bound) drug was considered, the CSF/plasma ratio for the diester, as well as for its major metabolite, MTX y-w-butyl ester, was indeed higher than the ratio for MTX. However, when account was taken of the fact that binding to plasma proteins was 90-95% for DBMTX as compared to only 50% for MTX, the ratios of total drug in the CSF and plasma compartments for the two compounds were not very different. A greater fraction of the injected dose of ester was excreted in bile than in urine, whereas the opposite was true for MTX. This was consistent with the idea that hepatic extraction is favoured for the lipophilic diester derivative in comparison with the more water-soluble parent acid. 

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