Drug Absorption

Biochemical/Physical Factors of Absorption

Surface area of absorbing surface

Other factors being equal, large surface areas will be able to absorb more of a drug than smaller surface areas

Duration of contact with absorbing surface

Drugs that are in contact with the absorbing surface for longer time periods will have more absorption than those with shorter contact times

• For example, patients with diarrhea will have less absorption of drug from the intestines.

Molecule Size

Larger molecules will be absorbed less readily than similar smaller molecules

Lipid Solubility

Lipid soluble drugs will diffuse across membranes more readily than ionized drugs

pH/pKa

• Diffusion across membranes requires drugs to be in an unionized form

• The pKa of a drug is the pH where half of the drug is in the ionized form and half of the drug is in the unionized form

• pH of the environment will impact the drug's ratio of ionized to unionized states.  

• You can use the Henderson-Hasselbalch equation to determine relative concentrations of ionized vs unionized forms at various pH levels. Stomach (pH 1.5-3.5) vs small intestine (pH 6-7.4)

Mechanisms of Absorption

Passive Diffusion

• Drug flows down concentration gradient (high concentration to low concentration)

• Not dependent on active transport or other mechanisms

• Not saturable

• May flow through channels or pores

Facilitated diffusion

• Transmembrane proteins that facilitate the drugs passage through membrane

• Drug flows down concentration gradient

• Saturable

Active transport

• Selective transport that requires energy (ATP)

• Mediated by transmembrane proteins

• May go against concentration gradient

• Example: P-glycoprotein

MDR1 (P-glycoprotein) – a gene that encodes for a transmembrane protein efflux pump that rids foreign chemicals from cells (moves foreign substances from cytoplasm out of the cell).

• These efflux pumps exist in many organs including kidneys and digestive system to rid the body of foreign substances.

• Neoplastic cells frequently express this protein, which contributes the cancer's resistance to chemotherapy.