Monkeys elimination

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). 

Unlike all other species, marmoset monkeys cannot metabolize iAs to methylated forms. During 4 days after i.p. administration of 0.4mg As Vkg, marmoset monkeys eliminated only 30% of the dose, mainly via urine (Vahter et al. 1982). As in urine and tissues of marmosets was iAs. Liver accumulated the largest portion of the dose (20%). Half of the liver As was bound to the rough microsomal membranes. No biotransformation (except of partial reduction of As to As ) was found after i.v. injection of 0.4mg As /kg (Vahter and Marafante 1985). Within 3 days posttreatment, about 39% of the dose was excreted in urine and only 2% in feces. Urinary As consisted of iAs and iAs present at a ratio of 1 1. The basis for the absence of iAs methylation in marmoset monkeys remains unknown. In contrast to the marmoset, other monkey species Cynomologus and Rhesus)... 

Prasad et al. [126] developed and used a sensitive and specific spectropho tome trie method for the estimation of primaquine to study the plasma kinetics of primaquine in Rhesus monkeys. It was observed that the drug completely disappeared from the plasma in 24 h after a single oral dose. Its concentration in the plasma reached a peak at 2 h of administration. The mean absorption and elimination half-lives were 0.36 0.08 and 3.44 0.37 h, respectively. 

Chu I, Villeneuve DC, Viau A. 1982. Tissue distribution and elimination of photomirex in squirrel monkeys. Bull Environ Contam Toxicol 29(4) 434-439. 

The disappearance of tritiated vindesine from the blood of rats has been reported to be biphasic, with half-life estimates of 15 min (distribution) and 10 hr (elimination) (59) it is likely that the prolonged elimination phase represents a hybrid between the second elimination phase described above for vincristine and the prolonged third phase evident on inspection of log concentration-time plots for vincristine in the rat. Biliary excretion contributes heavily to the elimination of vindesine in the rat. The bioavailability of vindesine in the rat appears to be very poor. The distribution of vincristine to different tissues in the mouse has been correlated with the estimated concentration of tubulin in the tissues (40). Tubulin concentration was measured by the capacity of a tissue to bind colchicine (40) comparable relationships between tissue concentrations of vincristine and colchicine binding capacity were observed for the dog and the monkey, but it should be emphasized that the correlations were based on the assumption that tissue tubulin content is closely similar in the mouse, dog, and monkey. 

McCollister DD, Beamer WH, Atchison GJ, et al. 1951. The absorption, distribution and elimination of radioactive carbon tetrachloride by monkeys upon exposure to low vapor concentrations. J Pharmacol Exp Therap 102 112-124. 

LaMantia, A.-S., and Rakic, P. (1994) Axon overproduction and elimination in the anterior commissure of the developing rhesus monkey. / Comp Neurol 340 328-336. 

The toxicokinetics of coumarin have been studied in a number of species including rats (intraperitoneal, intravenous, oral and topical administration) (Hardt Ritschel, 1983 Ritschel Hussain, 1988), dogs (intravenous and oral) (Ritschel Grummich, 1981), gerbils (intraperitoneal) (Ritschel Hardt, 1983) and rhesus monkeys (intravenous and oral) (Ritschel et al, 1988). Generally, the half-life for the elimination of coumarin is similar in all species examined, being around 1-4 h (Lake, 1999). In rats, the toxicokinetics of coumarin are non-linear at intraperitoneal doses greater than 10 mg/kg bw (Hardt Ritschel, 1983). 

Pharmacokinetics and cerebrospinal fluid penetration of hypericin were studied after i.v. dose of 2 mg/kg in monkeys (Table 2) (70). Mean peak plasma concentration of hypericin following this dose was 71.7pg/mL (142 pM). Elimination of hypericin from plasma was biexponential, with an average terminal half-life of 26 14 hours. The 2 mg/kg dose in nonhuman primates was sufficient to maintain plasma concentrations above 5.1 pg/mL (10 pM) for up to 12 hours (the in vitro concentration required for growth inhibition of human glioma cell lines is greater than 10 pM). 

Rozman KK, Rozman TA, Williams J, et al. 1982. Effect of mineral oil and/or cholestyramine in the diet on biliary and intestinal elimination of 2,4,5,2, 4, 5 -hexabromodiphenyl in the Rhesus monkey. J Toxicol Environ Health 9 611-618. 

In rats and monkeys, moderate absorption of diminazene has been reported following its oral administration. In studies with rabbits given the combination product at 3.5 mg/kg bw intramuscularly, maximum blood levels at 15 min and 3 h were 1.3 and 0.116 ppm, respectively. Tissue levels at 1 days after treatment were highest in the liver (40 ppm), brain (2.5 ppm), and kidney (3 ppm), whereas 40-50% of the administered was eliminated in the urine and 8-20% in the feces. 

Following oral administration of radiolabeled furosemide, excretion was reported to be almost complete within 3 days in rats (96-98%) and dogs (98-99%). Rat urine contained 40-50% of the parent drug, 30% 4-chloro-5-sulfamoyl-anthranilic acid, and four unidentified metabolites that accounted for the rest of the administered radioactivity. In contrast, urine of dog and monkey contained 85% unmetabolized furosemide, 7% 4-chloro-5-sulfamoyl-anthranilic acid, and the remainder was due to unidentified metabolites. Following intramuscular injection of 5 mg furosemide/kg bw in cattle, the half-life for plasma elimination was estimated at 4.3 h. In contrast, the half-life of furosemide in cattle was reported to be less than 1 h following intravenous administration. 

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). 

Comparative Toxicokinetics. A limited number of studies exist regarding the comparative toxicokinetics of orally administered silver compounds in rats, dogs, monkeys, and humans. A more complete comparison of the absorption and elimination of silver in humans and rats may be warranted given that much of the toxicokinetic data comes from rats. It would also be useful to acquire data on the comparative toxicokinetics of various silver compounds in several species of experimental animals and in humans following inhalation and dermal exposure in order to model the kinetics of silver deposition across different exposure scenarios and within sensitive populations. 

The pharmacokinetic profile of 2 -MOE partially modified ASOs was similar in mice, rats, dogs, monkeys, and humans in that the drug was cleared within hours from the plasma and distributed to the tissues. Following IV administration, the plasma concentration-time profiles of 2 -MOE partially modified ASO are poly-phasic, characterized by a rapid distribution phase (half-lives of 30-80 min), followed by at least one additional much slower elimination phase with half-lives reported from 10 to 30 days. The recent development of ultrasensitive hybridization ELISA methods have made it possible to follow plasma concentrations for up to three months after dose administration, enabling the investigators to determine terminal plasma elimination half-lives [24, 26, 30, 31]. Representative plasma concentration-time profiles with the rapid distribution phase along the slow terminal elimination phase in monkeys and humans for a 2 -MOE partially modified ASO, ISIS 104838 are shown in Figure 4.2 [26]. 

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