Drug metabolism developmental differences

It must be recognized that developmental differences in hepatic drug metabolism occur consequent to reductions in the activity of specific drug-metabolizing enzymes and their respective isoforms. For most enzymes, the greatest reduction of activity is seen in premature infants where immature function may also reflect continued organogenesis. This... 

The intended use of a chemical probe will necessarily dictate its desirable characteristics. Probes of cellular processes used for epistatic perturbations will be subject to some of the same limitations of an in vivo probe of zebrafish developmental patterning however, drug metabolism and pharmacokinetic (DMPK) parameters essential for the action of an in vivo probe used in mouse or rat will not necessarily apply to the function of a cellular probe. Indeed, these differences will alter priorities for the beneficial characteristics of an in vitro probe when compared to an in vivo probe. For example, Lipinski s rule of five remains a central tenet of medicinal chemistry in drug discovery which serves as a useful limit of molecular characteristics for the development of orally bioavailable drugs, and while these guidelines generally describe preferable probe molecule properties, the rule of five may be... 

The effects of a chemical in a tissue frequently depend on the chemical s interaction with cell surface or cytoplasmic receptors. In some cases, a chemical interacts directly with the cell membrane and alters its permeability. The pharmacodynamic actions of drugs are usually mediated by interactions with a receptor, and a drug often competes with endogenous ligands of a receptor. The toxicity of environmental chemicals can also depend on and be mediated by interactions with receptors. In some cases, the responses are different for chemical exposures at different fetal stages of development, and it is possible to explain the different responses by the chronology of the development of fetal receptor systems. The fetus may develop receptor systems for a compound before it develops the ability to metabolize that compound thus, a low level of an active chemical can have greater and more persistent effects in the fetus than in the mother, whose metabolism limits the duration and extent of the effect. This is one mechanism for selective developmental toxicity of chemicals. 

Developmental changes produce differences in the absorption, metabolism and excretion of drugs. These age-related changes in pharmacokinetics have been used as determinants in the development of age-specific dose recommendations. 

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