Pharmacokinetics 2 Flashcards
the larger the therapeutic range…
depends on how well the drug has been absorbed
For drugs reaching target via blood/plasma (systemic circulation):
“the magnitude of drug effect is associated to [drug] available in the plasma/blood)”
first order kinetics
concentration and rate in proportion
zero order kinetics
conc and rate NOT in proportion
Such kinetics may not be TRUE, if
the drug effect is mediated through a metabolite
the drug effect is irreversible
follow different kinetics in the target compartment (different from blood)
Passive diffusion
Major mechanism of drug delivery
Depends on the ability of drug (physiochemical characteristics) crossing lipid bilayer membrane
[most drugs gets absorbed by passive diffusion]
Active diffusion
Require transporter/carrier for the uptake of drug across cell membrane
Rate of diffusion
(PD)
surface area
-thickness of membrane
-molecular size & lipid solubility
(diffusion constant)
[D] amount transfer
(PD)
Transfer rate
Residence time at membrane
Low lipid soluble (hydrophilic) drugs use transporters
(AD)
Organic anion transporters (OATs)
Organic cation transporters (OCTs)
(also covered in urinary system lectures)
what kind of drugs will ONLy pass through lipid bi-layers?
un-ionised
Weak acids or weak bases
Equilibria between
AH A- + H+ [Acid]
B + H+ BH+ [Base]
(un-ionized) (ionized)
What are the Factors affecting ionisation?
pH (i.e. concentration of H+ ions)
pKa of drug
(pH at which 50% of molecules are in each state)
pH mouth 7.4
stomach 1.5
Intestine 5.3
Factors influencing G. I. absorption (physiological)
G.I. motility
- G.I. secretions & enzymes
- drug-food/supplement interactions
Advantages of G. I absorption (physiological)
Large surface area for passive diffusion
Range of pH environments promote uptake of weak acids/bases
Richly vascularised (high blood supply)
Long tract and long dwell time
Some active transport (e.g. Levodopa taken up by phenylalanine transporter)
Small intestine is a major site for drug absorption
How well a drug absorbed in the body?
(efficiency of drug absorption)
Bioavailability (F): measure of proportion of dose absorbed, compared to I. V. (same) dose
F= AUC of oral/AUC of I.V (for oral drug)
Time to peak (tmax): time required to reach maximum drug concentration in plasma (is a measure of rate of absorption)
tmax (oral)= 25 min
when acid gets put in drug it will become IONISED WHICH MEANS…..
it WILL NOT pass through lipid bilayer membrane
weakly acidic
unionised drug - effective absorption
Administration & Absorption: Summary
Most common route of administration is through oral
Major site of drug absorption is small intestine.
Drug absorption from sites, muscle, skin, lungs and others can bypass GI tract
The rate of absorption depend on the
- Vascularisation of site of absorption
- Characteristics of formulation/dosage forms
lipid solubility of the drug
- pH of the site of absorption
AUC
area under curve
