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Variability in Xenobiotic Transformation (Exam 2)
Terms in this set (15)
Differences in relative rates or quantities of a xenobiotic biotransformed by a specific pathway
The presence or absence of a specific xenobiotic biotransformation pathway
How does age impact xenobiotic transformation?
Given the example of P450, it is lowest in a growing fetus, but exponentially grows until adolescence. From there, it plateaus until becoming elderly, where it starts to decline.
What are canine's deficient in?
What are felines and Gunn rats deficient in? Both are specifically poor in what?
Some glucuronyl transferases
Cats are specifically poor in glucuronidation of phenolics
Gunn rats are specifically poor in glucuronidation of bile acids.
What are porcine's and opossum's deficient in?
What are guinea pig's, chicken's, swine and human's deficient in?
Mercapturic acid synthesis
What is different about conjugation with birds and reptiles?
They conjugate primarily with ornithine instead of other amino acids.
How does amphetamine differ across a variety of species (carnivores, rodents, primates, humans, equine)?
Causes a wide variety of rate differences.
Carnivores and rodents -primarily oxidation
Primates -primarily deamination
Human -urine pH dependent excretion
Equine -no pH dependency of excretion
How does aniline (aminobenzene) differ across a variety of species (vertebrates, carnivores, birds and rats)?
Vertebrates - no meta-hydroxylation-species dependent amounts of para-and ortho-hydroxylation
Carnivores - typically more ortho-
Birds and rats - typically more para-
What are the kinetics of xenobiotic transformation?
Rate of change from substrate (A) to metabolite (B) - rate of drug transformation (loss) is generally limited to the loss of the parent compound, as the metabolites may not be known or may be difficult to quantify.
What is a zero-order reaction?
Amount of drug is decreased at a constant amount per unit time. A direct plot of A vs. time yields a straight line.
What is a first-order reaction?
Amount of drug is decreases at a rate that is proportional to the amount of drug remaining. A plot of Log A vs. time yields a straight line.
What occurs when you have multiple reactions?
Non-linear decreases in a drug and can also occur with multi-compartment distribution Requires curve stripping to calculate reaction OR elimination rates (primary, secondary, tertiary, etc.)
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