Pharmacokinetics
8 important questions on Pharmacokinetics
The degree of dissociation of the drug is dependent on (2 factors):
- pH of the environment
What is the partition-coefficient (log P)
It says something about the lipophilicity of a substance. The higher log P, the more lipophilic the substance.
Phase I reactions: Functional reactions (4 characteristics)
- Oxidation, reduction, hydrolysis
- Metabolites are polar/hydrophilic
- Metabolites can be inactive or active
- Metabolites sometimes participate in phase II reactions
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Phase II reactions: Coupling reactions (4 characteritics)
- glucuronidation, acetylation
- Metabolite is always hydrophilic and inactive after the reaction
- Can take place without phase I reaction
- The metabolite is usually excreted by the liver, through the bile
Cytochrome P450 system
- Oxidative enzymes (microsomal enzymes)
- Expressed in ER
- Cytochrome P450: iron-containing proteins
- Expressed mostly in liver/intestines
- Broad specificity (chance of competition between drugs)
Called CYP enzymes. The substrate binds the iron part of the enzyme and is then metabolized. 3 different families, 6 subfamilies
Two factors influencing biotransformation
- Enzyme inhibition
Biological availability (F)
Depends on:
- Absorption, good absorption higher F
- Biotransformation, poorly metabolized means higher F
Inducer would mean a lower biological availability
Working dose (formula)
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