LEC 23 Clinical Pharmacokinetics I Flashcards
What is the significance of P-gp (MDR-1) in relation to drug absorption?
- P-glycoprotein (P-gp) expels drugs from cells and organs, preventing penetration
- Distributed in intestinal epithelium where it pumps drugs back into the lumen
- Reduces the drug’s efficacy, bc the cells are trying to get it excreted
- Present in both prokaryotes and eukaryotes
What do phase I metabolites of a drug generally contain and why is it important?
Substituent group added?
Usually involves the addition of hydroxyl groups to the drug in order to make it more water soluble for conjugation and secretion
What is the most important enzyme for catalyzing the phase I reactions in drug metabolism?
Cytochrome P450 (CYP)
Flavin-containing monooxygenases (FMOs) are also important
Which enzymes catalyze the phase II (transferase) reactions in drug metabolism?
- Glutathione S-transferase
- UDP-glucoronyltransferases
- Sulfotransferases
- N-acetyltransferases
- Methyltransferses
Where in the cell are the enzymes that are inducible by drugs located?
Smooth ER
What is pharmacodymanics?
What the drug does to the body
What is pharmacokinetics?
What the body does to the drug
ADME
In order to calculate the half life of a two compartment model, what must be taken into account?
The distribution must reach equilibrium before your can calculate the half life
What is the equation for half-life?
Generally speaking, about how many half lifes does it take to eliminate a drug?
4-7 half lifes
What does the volume of distribution tell us?
Provides a quantitative measure of the extent of distribution of a drug out of the blood stream
Volume of distribution (Vd) is equal to the sum of what other volumes?
Vc (volume of central compartment) + Vp (volume of peripheral compartment)
How do you calculate Vd for an intravenous administration?
Lambda n is the slope of elimination curve
How do you calculate Vd for an oral administration?
Lambda n is the slope of elimination curve. F is bioavailability
How do you calculate the amount of drug in the body?
Plasma concentration x Vd
