52
Biotransformations of Drugs and Chemicals
Keywords
Electrophilic
A compound, group, or function that is electron deFcient and therefore preferentially
reacts with electron-rich moieties.
Endobiotic
A compound that is endogenous to the organism.
LogP
The log of the partition coefFcient for a compound between an organic solvent, often
octanol, and water.
Nucleophilic
A compound, group, or function that is electron rich and therefore preferentially reacts
with electron-deFcient moieties.
Prodrug
A structure without a desired pharmacological property that is converted by
metabolism to a product that has the desired property.
Xenobiotic
A compound foreign to the organism.
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Drug and xenobiotic metabolism converts the lipophilic compounds that can
be absorbed into the body into polar, excretable products, thus preventing their
accumulation, but also sometimes forms more toxic products.
1
General Purpose of Xenobiotic and Drug
Metabolism
Life is based on the organization of biologi-
cal systems into compartments segregated
by means of lipid bilayer membranes. This
applies to subcellular organelles such as
the nucleus and mitochondria, to the cells
themselves, and through the assembly of
cells into surfaces, to organs, and larger
entities. The membrane barriers prevent
the passage of charged or highly polar
molecules, with the exception of small
molecules that diffuse through pores in the
membrane barriers, molecules for which
active transport systems exist, or molecules
taken up during pinocytosis. Lipophilic
molecules can cross the membrane bar-
riers relatively unimpeded unless they
are so lipophilic that they are effectively
trapped within the membrane. In contrast,
mammals and other complex organisms
only efFciently excrete polar or ionic com-
pounds because lipophilic compounds are
readily reabsorbed from excretory com-
partments such as the kidney. Thus, the
properties that allow a xenobiotic to be
taken up by a biological system are the
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