Absorption, distribution, metabolism elimination studies

Pharmacokinetic/ ADME (absorption, distribution, metabolism, elimination) studies including bioanalytical method development... 

No data were located concerning whether pharmacokinetics of endosulfan in children are different from adults. There are no adequate data to determine whether endosulfan or its metabolites can cross the placenta. Studies in animals addressing these issues would provide valuable information. Although endosulfan has been detected in human milk (Lutter et al. 1998), studies in animals showed very little accumulation of endosulfan residues in breast milk (Gorbach et al. 1968 Indraningsih et al. 1993), which is consistent with the rapid elimination of endosulfan from tissues and subsequent excretion via feces and urine. There are no PBPK models for endosulfan in either adults or children. There is no information to evaluate whether absorption, distribution, metabolism, or excretion of endosulfan in children is different than in adults. 

Hansch and Leo [13] described the impact of Hpophihdty on pharmacodynamic events in detailed chapters on QSAR studies of proteins and enzymes, of antitumor drugs, of central nervous system agents as well as microbial and pesticide QSAR studies. Furthermore, many reviews document the prime importance of log P as descriptors of absorption, distribution, metabolism, excretion and toxicity (ADMET) properties [5-18]. Increased lipophilicity was shown to correlate with poorer aqueous solubility, increased plasma protein binding, increased storage in tissues, and more rapid metabolism and elimination. Lipophilicity is also a highly important descriptor of blood-brain barrier (BBB) permeability [19, 20]. Last, but not least, lipophilicity plays a dominant role in toxicity prediction [21]. 

Toxicokinetic—The study of the absorption, distribution, metabolism, and elimination of toxic compounds in the living organism. 

Absorption, Distribution, Metabolism, and Excretion. No studies were located regarding the absorption, distribution, metabolism, and excretion of disulfoton by humans or animals after inhalation or dermal exposure. Limited data exist regarding the absorption, distribution, and excretion after oral exposure to disulfoton. Data on levels of disulfoton and metabolites excreted in urine and expired air suggest that some almost complete absorption of an administered dose of disulfoton over 3-10 days (Lee et al. 1985 Puhl and Fredrickson 1975). The data are limited regarding the relative rate and extent of absorption. Animal data suggest that disulfoton and/or its metabolites are rapidly distributed to the liver, kidney, fat, skin, muscle, and brain, with peak levels occurring within 6 hours (Puhl and Fredrickson 1975). Elimination of disulfoton and metabolites occurs primarily in the urine, with >90% excreted in the urine in 3-10 days (Lee et al. 1985 Puhl and Fredrickson 1975). 

Studies of dmg absorption, distribution and elimination comprise what is referred to as pharmacokinetics. By contrast, the concentration of a pharmaceutical compound at the site(s) of action in relation to the magnitude of its effect(s) is referred to as pharmacodynamics. Both pharmacokinetics and pharmacodynamics have their roots in physiology, chemical kinetics, biochemistry, and pharmacology. They seek to provide a mathematical basis of the absorption, distribution, metabolisms, and... 

Propiopromazine has been used in all the domesticated animals. Although very limited information is available on the absorption, distribution, metabolism, and elimination of propiopromazine in animals, several studies (103) have reported the presence of propiopromazine in pig kidney collected from abattoirs, so that human exposure should therefore be presumed. Both pigs and horses are able to metabolize propiopromazine, at least in part. The drug binds extensively to tissue proteins, and also accumulates in fatty tissues. 

Pharmacokinetics is the study of how the body affects an administered drug. It measures the kinetic relationships between the absorption, distribution, metabolism, and excretion of a drug. To be a safe and effective drug product, the drug must reach the desired si te of therapentic activity and exist there for the desired time period in the concentration needed to achieve the desired effect. Too little of the drug at such sites yields no positive effect (MTC) leads to toxicity. For intravenous administration there is no absorption factor. Total body elimination includes both metabolic processing and excretion. 

Profiling of Drug Absorption, Distribution, Metabolism and Elimination in Man the hADME Study... 

The aim of this kind of study is to characterize the Absorption, Distribution, Metabolism and Elimination of the investigational product in humans (hADME study), following an administration of the compound in a radiolabeled form. The use of a radiolabel allows identifying metabolites, which were not known beforehand, and to characterize them. In addition, using a radiolabel is - in most cases - the only way to establish a complete balance of the drug and its metabolites, which is required to validate the completeness and predicitvity of the results. 

Toxicokinetics describe Absorption, Distribution, Metabolism and Elimination (ADME) of a chemical in humans, experimental animals or cellular systems. Of specific importance for interpretation of animal studies and for extrapolation of hazards between species is the comparative information on the exposure and the dose that reaches the critical target. 

The toxicokinetics of benzene has been extensively studied. Inhalation exposure is probably the major route of human exposure to benzene, although oral and dermal exposure are also important. Absorption, distribution, metabolism, and elimination have been studied in both humans and animals. Investigations of the metabolism of benzene have led to the identification of toxic metabolites, and to hypotheses about the mechanism of toxicity. 

Accurate exposure and biological monitoring data are crucial to the evaluation of residential exposure and risk estimates since the potential health risks associated with a pesticide depend on the amount of exposure to the pesticide, its toxicity and the susceptibility of the exposed population. Prediction of whether adverse health effects will occur in humans can be made by comparing the exposure estimate to the No Observed Adverse Effect Level (NOAEL) derived from the animal toxicity data. Uncertainty arises from the input data used in an assessment, e.g. variability in time-activity patterns, contact with exposure media, bioavailability, exposure duration, frequency of product use and differences in the route of exposure in humans from that in the animal studies (since absorption, distribution, metabolism and elimination kinetics may differ substantially by exposure route). 

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