Bioavailability for a Drug if its Elimination is First-Order

Same drug and three different formulations

Toxic level
1. Compare Cmax and Tmax
2. Compare duration of action
Therapeutic Level
3. Compare Intensity of action
4. Compare onset of action
5. Compare rate of absorption
6. Compare termination of action

( | =1 min)

Three brands of the same drug with same AUC

What does the term "same AUC" mean?

Why don’t the absorption phase of the three
lines match since the same drug has same
absorption mechanism?
 Mechanisms of Drug Permeation

Passive diffusion through aqueous channels in the intracellular junctions (filtration)(A)

Passive diffusion through lipid cell membranes ( B)
Special Carries: Active Transport or Facilitated Diffusion (C )
Endocytosis and Exocytosis (D)
 Mechanisms of Drug Permeation
Passive Diffusion : two types
through aqueous channels or through lipid cell membranes
Its that not require cellular energy or assistance
Aqueous diffusion: occurs within the larger aqueous
compartments of the body: interstitial space, cytosol, across
epithelial membrane, aqueous pores the endothelia lining of
blood vessels
Lipid diffusion: lipid-aqueous partition coefficient of the
drug determinesthe rate of diffusion

Determinants of Diffusion rate

The concentration gradient across the
Aqueous or Lipid solubility
membrane (driving Force)
The area of absorptive surface (**lipids)
Molecule size (**aquous)
Degree of ionization (** lipid) 14
 Rate of Diffusion Across Membranes: Fick’s Law

Permeability of membrane: Ability of the substance to move either through the small pores
in the membrane or the lipophilic interior of the membrane
For lipid diffusion, the partition coefficient determines how readily the drug enters the lipid
membrane from the aqueous medium (Permeability); it is a major determinant of flux
The higher the portion coefficient , the more lipid soluble, the faster the rate of transfer
across biological membranes
Fick’s Law applies to a situation where there is an absence of factors such as: ionic, pH,
charge gradients across the membranes .
 pH Tapping Across Lipid Bilayers
Weak acid drugs:
Phenobarbital, aspirin

Henderson-Hasselbalch Equation

Weak acid: a neutral molecule that can reversibly dissociate into an anion (-) and a proton
(H+) (aspirin or acetaminophen).
Need to become protonated (uncharged) to be more lipid soluble

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