Drug Absorption and Oral Route I Flashcards
What is the goal of pharmaceutics?
Right dose, right time, correct duration, and not to reach other sites in the body where drug toxicities occur
What is the area of study embracing the relationship between the physical, chemical, and biologic sciences as they apply to drugs, dosage forms, and drug action.
Biopharmaceutics
Cell membranes mostly bear a _____ charge on surface
negative
Cell membrane is _____ permeable
selectively
Process by which a compound and its metabolites are transferred from GI tract to circulating system (parent + metabolites) describes what?
Absorption
Passive diffusion is governed by the ______ ______
concentration gradient
The concentration gradient governs what kind of diffusion?
Passive
What is the main difference between active and facilitated transport?
Facilitated transportation does not go against a concentration gradient
Active transport:
Concentration ____ to _____
needs _____ and ____
Low + High
Carrier + energy
Passive diffusion:
Concentration ____ to ____
no ____
High + Low
No carrier/energy
Paracellar transport:
Concentration ____ to ____
no ______
High + Low
No Carriers
Facilitated diffusion:
Concentration ____ to ____
Needs ____ but no ____
High + Low
Carrier + No energy
What kind of cells do drugs go through when entering to the lymph?
M cells
When drugs go through M cells, lipids and particles take what kind of transport rather than intestinal absorption?
Transceullular
What is Fick’s first law?
Describes passive diffusion; rate of diffusion across a membrane at a steady-state flow
What is the most important physical property of a drug in relation to its ADME?
Lipophilicity
_______ is a movement of molecules from one phase to another, e.g. from aqueous to lipid, from liquid to a plastic of container, from outside to inside of a membrane
Partitioning
______ : P (or K) is a measure of a molecule’s lipophilic character, indicating its preference for hydrophilic or lipophilic phase.
Partition coefficient
What is typically used as the nonaqueous phase in the partition experiment?
Octanol
What is typically used as the aqueous phase in the partition experiment?
Water
For partitioning, increase of octanol, will P increase or decrease
Increase; molecule is more like the lipid phase
pH of the GI fluid could change what?
- Solubility
- pH-partition hypothesis
- Chemical stability
Degree of a drug’s ionization depends on what?
pH of environment + pKa of drug
Most drugs are absorbed thru GI tract by _____ diffusion
passive
Lots of H+ bonds or ionic bonds with water is favorable for diffusion (T/F)
False; unfavorable
Lipinski’s Rule of 5
Molecular weight should be…
<500
Lipinski’s Rule of 5
logP should be at….
<5
Lipinski’s Rule of 5
How many H-bond donors should there be?
<5
Lipinski’s Rule of 5
How many H-bond acceptors should there be?
<10
In sink conditions, Fick’s first law changes what?
C2 = 0
Where is C1 + C2 found?
C1 = GI tract C2 = Blood
What is the sink condition equation under Fick’s first law?
- dc/dt = P(C1-C2)
- dc/dt = P(C1) (sink condition)
What is the permeability coefficient equation?
-dc/dt = DSK/h * C1
-dc/dt = DSK/h * C1
What is h?
Thickness of absorbing membrane
-dc/dt = DSK/h * C1
What is S?
Area of absorbing membrane
-dc/dt = DSK/h * C1
What is K (or P)?
Partition coefficient, measure of permeability of the membrane to the drug
-dc/dt = DSK/h * C1
What is D?
Diffusion coefficient of drug
pH Saliva
6.4
pH stomach (fasting)
1.4 to 2.1
pH stomach (fed)
3 to 7
pH duodenum (fasting)
4.4 to 6.6
pH duodenum (fed)
5.2 to 7.2
pH jejunum + ileum
6.5 to 8
pH colon
7 to 7.5
pH urine
5.5 to 7
