Drug biotransformation physicochemical properties

A description of transdermal drug delivery has been produced which is based on the physicochemical properties of the permeant. At this time transdermal delivery is limited to the administration of potent drugs. Higher doses may be accessible if penetration enhancers are incorporated into the formulation. The kinetic model shows what properties these should have and that they are a function of the physico-chemical properties of the drug. Various loss processes, e.g. microbial biotransformation, skin enzyme metabolism can be identified but cannot, as yet, be quantified. 

Drug design must not only take into account the chemical and physicochemical properties which relate to intrinsic drug potency, but also those properties which relate to the ability of molecules to reach, and remain at, the site(s) of action in vivo. Clearly, properties such as rate and extent of absorption, distribution, biotransformation, and excretion have to be considered in drug design. 

Predictions of drug metabolism based on quantitative structure-metabolism relationships (QSMRs), expert systems, and molecular modeling of enzymatic sites The consequences of such reactions on activation and inactivation, toxification, and detoxification Prodrug and soft drug design Changes in physicochemical properties (pKa, lipophilicity, etc.) resulting from biotransformation... 

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