Kidneys neonatal animals

The limited toxicity data available for endosulfan suggest that several subgroups of the population may be more susceptible to endosulfan exposure than the general population. These subgroups include the unborn and neonates the elderly and people with liver, kidney, or neurological diseases, - effects that have been better characterized in animal studies. 

The main rout of excretion of the drug and its metabolites is the kidney with a half-life of 9-18 h in human. In contrast to human, animal models have a lower elimination half-life ranging from 0.6-9 h [78]. The elimination half-life of valproic acid and some metabolites was found to be much longer in the neonates (40-50 h) than adult subjects (9-18 h) [78,81]. One study reported no difference between the elimination half-life between elderly and young subjects (15.4 and 13.0 h, respectively) while other found an increase in for older patients (14.9 versus 7.2 h for young patients) [78,90], Insignificant amounts of valproic acid are found in breast milk, approximately 3% of maternal drug levels [84]. 

Results from animal studies indicate that while furosemide enhanced cephaloridine nephrotoxicity no increased renal toxicity was observed by combining of piperacillin with furosemide [142]. Latamoxef and flo-moxef may decrease nephrotoxicity of vancomycin by inhibiting its uptake into the kidney [146,147]. The results of a retrospective study including renal transplant patients indicate that aztreonam can be safely administered with cyclosporine [148]. Combination therapy with ampicillin/aztreonam in neonates showed a lower renal toxicity than in the group with concurrent administration of oxacillin/ amikacin [149]. 

Data are limited on elimination of metallic and inorganic mercury in animals. Initial excretion of mercury is predominantly in the fecal matter following inhalation of metallic mercury vapor, but as mercury concentrations increase in the kidneys, urinary excretion increases (Rothstein and Hayes 1964). After inhalation, approximately 10-20% of the total excreted metallic mercury is by exhalation (Rothstein and Hayes 1964). Mercury is excreted in the urine of mice exposed orally to mercuric sulfide ( 8-200 mg Hg/kg) (Yeoh et al. 1986, 1989). The amount of mercury in the urine of the treated group was 4.5-15-fold greater than the control levels. Urinary rates of mercury excretion were 1.6-2.2 ng/hour. Neonatal rats (1, 8, and 15 days old) eliminated mercury slower than older rats (22 and 29 days old) given mercuric chloride subcutaneously (Daston et al. 1986). 

The plastic nature of immature organs such as kidney, liver, brain and lung may indicate the need for more animal toxicology. Frequently, neonatal acute and subacute toxicology studies are undertaken in two animal species. Because of the small size of both mouse and rat pups, this may prove a challenge to administer the active drug. The common mixing with chow is inappropriate in neonates. Dog pups usually provide one of the two species, so a special liquid formulation for... 

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