Membrane Transport of Drugs involves processes like passive diffusion, facilitated diffusion, active transport, and endocytosis for drug movement across cell membranes.
Membrane Transport of Drugs
Understanding how drugs cross biological membranes is crucial to all processes of pharmacokinetics (ADME).
Biological membranes are primarily lipid bilayers interspersed with proteins.
Several mechanisms allow drugs to traverse these membranes:
Passive Diffusion
Most common mechanism for many drugs.
Dependent on the concentration gradient (high → low).
Does not require energy.
Best suited for lipid-soluble (lipophilic) drugs that can easily pass through the hydrophobic core of the membrane.
Rate is influenced by: lipid solubility, degree of ionization (pKa), molecular size, thickness of the membrane, and the area of absorption.
Facilitated Diffusion
Utilizes a carrier protein or a specific transporter embedded in the membrane.
Moves drugs down the concentration gradient (no direct energy required).
Saturable and subject to competition (different substances may use the same transporter).
Active Transport
Also uses carrier proteins but can move drugs against their concentration gradient.
Requires energy (ATP) directly or indirectly.
Saturable and can be inhibited by substances competing for the same transporter.
Example: transport of levodopa across the blood-brain barrier via amino acid transporters.
Endocytosis and Exocytosis
Endocytosis: The cell membrane engulfs the drug particle (often larger molecules like protein drugs) forming a vesicle.
Exocytosis: The vesicle fuses with the cell membrane to release its contents outside the cell.
Examples: Vitamin B12 absorption in the gut involves receptor-mediated endocytosis.
Ion-Pair Transport
Some highly ionized drugs can form neutral complexes (ion pairs) with endogenous substances that facilitate passive transport across membranes.