Absorption, distribution, metabolism research studies

Although there is no reason to suspect that the pharmacokinetics of 1,4-dichlorobenzene differs in children and adults, scant data are available to support or disprove this statement. Studies of absorption, distribution, metabolism, and excretion in children would aid in determining if children are at an increased risk, particularly if conducted in an area where a high-dose acute or low-dose chronic exposure to an environmental source were to occur. With regard to exposure during development, additional research on maternal and fetal/neonatal toxicokinetics, placental biotransformation, the mechanism of... 

Absorption, Distribution, Metabolism, and Excretion. The database for inhalation and dermal absorption of silver compounds in humans consists primarily of qualitative evidence from occupational case studies. Limited quantitative information exists on the oral absorption of silver compounds in humans. Research into the quantitative absorption of various silver compounds following relevant exposure routes would be useful to better predict the potential for toxic responses to particular silver compounds in humans. 

Biomonitoring study design should consider absorption, distribution, metabolism, and elimination in selection of appropriate biomarkers to address the goals of research and surveillance. 

As was noted in Chapter 4, pharmacokinetic and pharmacodynamic effects are studied in nonclinical research. These topics are also of critical importance in clinical investigations. A drug s pharmacokinetics and pharmacodynamics are of considerable interest to clinicians who may prescribe the drug to patients once it is approved. Meaningful decisions about a drug s optimal use can only be made with an understanding of the time course of events that occur after the drug s administration, and both pharmacokinetics and pharmacodynamics are concerned with this time course. By consideration of the pharmacokinetic processes of absorption, distribution, metabolism, and excretion (ADME), the... 

More recently, partially as a result of increased research sophistication and observations made in ADME (Absorption, Distribution, Metabolism, and Excretion) studies, increased attention is being given to evaluating metabolites of APIs. An old example (not being pursued because of the lack of patent protection) is the metabolite... 

Comparative Toxicokinetics. Qualitatively, absorption, distribution, metabolism, and excretion appear to be similar in humans and laboratory animals. However, quantitative variations in the absorption, distribution, metabolism, and excretion of benzene have been observed with respect to exposure routes, sex, nutritional status, and species. Further studies that focus on these differences and their implications for human health would be useful. Additionally, in vitro studies using human tissue and further research into PBPK modeling in animals would contribute significantly to the understanding of the kinetics of benzene and would aid in the development of pharmacokinetic models of exposure in humans. These topics are being addressed in ongoing studies (see Section 2.10.3). 

The available toxicokinetic data did not evaluate the potential differences between adults and children, although there is some evidence that there are age-related differences in the activity of at least one enzyme, UDP-glucoronsyltransferase, that is involved in the metabolism of di- -butyl phthalate. Toxicokinetic studies examining how aging can influence the absorption, distribution, and excretion of di- -butyl phthalate would be useful in assessing children s susceptibility to di- -butyl phthalate toxicity. The mechanism of action for a number of toxic effects have not been elucidated. There are no data to determine whether there are age-specific biomarkers of exposure or effects or any interactions with other chemicals that would be specific for children. There is very little available information on methods for reducing di- -butyl phthalate toxic effects or body burdens it is likely that research in adults would also be applicable to children. 

Drug disposition and metabolism are of essential significance in pharmaceutical research because of the interdependence of pharmacokinetic and pharmacodynamic processes. Limited intestinal absorption, inadequate distribution, fast metabolism, and toxic metabolites are some of the causes of failure of drug candidates during development. To reduce the rate of attrition resulting from such pharmacokinetic defects, disposition and metabolic studies should be initiated as early as possible in the screening of lead candidates. 

---