Drug absorption is crucial for pharmacological effects. It involves the movement of drugs from administration sites to the bloodstream through biological membranes. Various mechanisms, including passive diffusion , facilitated diffusion , active transport , and endocytosis , facilitate this process.
Many factors influence drug absorption. These include physicochemical properties like lipophilicity and molecular size, physiological factors such as blood flow and pH, and the presence of transporters . Understanding these factors is essential for optimizing drug delivery and predicting drug behavior in the body.
Drug Absorption Mechanisms
Passive and Facilitated Diffusion
Top images from around the web for Passive and Facilitated Diffusion Passive transport - Wikipedia View original
Is this image relevant?
Facilitated diffusion - Wikipedia View original
Is this image relevant?
The Cell Membrane | Anatomy & Physiology I View original
Is this image relevant?
Passive transport - Wikipedia View original
Is this image relevant?
Facilitated diffusion - Wikipedia View original
Is this image relevant?
1 of 3
Top images from around the web for Passive and Facilitated Diffusion Passive transport - Wikipedia View original
Is this image relevant?
Facilitated diffusion - Wikipedia View original
Is this image relevant?
The Cell Membrane | Anatomy & Physiology I View original
Is this image relevant?
Passive transport - Wikipedia View original
Is this image relevant?
Facilitated diffusion - Wikipedia View original
Is this image relevant?
1 of 3
Drug absorption involves movement of drug molecules from administration site to bloodstream through biological membranes
Passive diffusion drives drug absorption without energy expenditure
Drugs move from high to low concentration areas
Occurs for many small, lipophilic molecules
Facilitated diffusion uses carrier proteins to assist transport
No energy input required
Typically used for larger or charged molecules
Examples: glucose transporters, ion channels
Lipid bilayer structure of cell membranes impacts absorption
Lipophilic drugs (ibuprofen) cross more easily than hydrophilic ones (metformin)
Active Transport and Endocytosis
Active transport moves drugs against concentration gradient
Requires energy and specific carrier proteins
Used for essential nutrients and some drugs
Examples: sodium-potassium pump, amino acid transporters
Endocytosis involves cells engulfing substances
Used for absorption of large molecules or particle-based formulations
Types include phagocytosis and pinocytosis
Example: absorption of vitamin B12 in ileum
Exocytosis expels substances from cells
Can be involved in secretion of drugs or metabolites
Example: neurotransmitter release at synapses
Factors Influencing Drug Absorption
Physicochemical Properties and Surface Area
Lipophilicity affects membrane crossing ability
Highly lipophilic drugs (benzodiazepines) absorb more readily
Hydrophilic drugs (metformin) have limited passive diffusion
Molecular size impacts absorption rate
Smaller molecules generally absorb faster
Large molecules may require specialized transport mechanisms
Ionization state determined by drug pKa and environmental pH
Unionized forms typically absorb more readily
Example: weak acids absorb better in stomach, weak bases in intestine
Surface area available for absorption varies by administration route
Small intestine provides largest surface area for oral drugs
Enhanced by presence of villi and microvilli
Transdermal absorption limited by skin surface area
Physiological Factors and Disease States
Blood flow to absorption site impacts drug uptake rate
Highly perfused areas (lungs, brain) allow faster absorption
Exercise can increase blood flow and enhance absorption
pH at absorption site alters drug ionization
Gastric pH (1-3) different from intestinal pH (6-8)
Can affect proportion of drug available for absorption
Presence of food in gastrointestinal tract influences absorption
Can alter gastric emptying time (delayed with high-fat meals)
May change pH or directly interact with drug
Example: tetracyclines chelate with calcium in dairy products
First-pass metabolism in liver reduces oral drug bioavailability
Significant for drugs like morphine and propranolol
Can result in much lower systemic exposure than administered dose
Disease states affecting organ function alter absorption patterns
Gastrointestinal disorders (Crohn's disease) may reduce absorption
Liver disease can impair first-pass metabolism
Altered pH in conditions like achlorhydria impacts ionization
Transporters in Drug Absorption
Influx and Efflux Transporters
Transporters facilitate movement of specific molecules across barriers
Specialized proteins embedded in cell membranes
Play crucial role in absorption of many drugs and nutrients
Influx transporters actively move drugs into cells
Enhance absorption of certain compounds
Examples: organic anion transporting polypeptides (OATPs), peptide transporters
OATP1B1 involved in statin uptake in liver
Efflux transporters pump drugs out of cells
Can limit absorption and contribute to drug resistance
P-glycoprotein (P-gp) is a well-known efflux transporter
P-gp limits absorption of drugs like digoxin and paclitaxel
Transporter expression and activity vary among individuals
Genetic polymorphisms can affect drug absorption and efficacy
Example: variations in SLCO1B1 gene affecting statin pharmacokinetics
Some drugs induce or inhibit transporter activity
Can lead to drug-drug interactions affecting absorption
Example: rifampicin induces P-gp, reducing digoxin absorption
Transporter-mediated absorption is saturable
Can result in non-linear pharmacokinetics at high concentrations
Important consideration for drugs with narrow therapeutic index
Understanding transporter mechanisms crucial for drug development
Informs strategies to enhance bioavailability
Allows targeting of specific tissues
Example: developing P-gp inhibitors to enhance brain penetration of certain drugs
Pharmaceutical form significantly influences dissolution and absorption
Tablets , capsules, solutions have different absorption profiles
Solutions generally absorb faster than solid dosage forms
Immediate-release formulations designed for rapid absorption
Quick onset of action for drugs like analgesics
Example: regular release acetaminophen tablets
Modified-release formulations control rate and site of drug release
Include extended-release, delayed-release, and targeted-release
Examples: enteric-coated aspirin, extended-release metformin
Particle size in solid dosage forms affects dissolution rate
Smaller particles generally allow faster dissolution
Micronization used to enhance absorption of poorly soluble drugs (griseofulvin)
Novel Delivery Systems and Bioequivalence
Excipients impact absorption by altering drug properties
Can change solubility , stability, or membrane interaction
Example: cyclodextrins enhancing solubility of lipophilic drugs
Novel drug delivery systems enhance absorption
Nanoparticles and liposomes protect drug from degradation
Can target specific absorption sites
Examples: liposomal amphotericin B, nanoparticle-based cancer drugs
Route of administration directly impacts absorption process
Oral, transdermal, parenteral routes have distinct absorption profiles
Influences bioavailability of the drug
Example: transdermal fentanyl patch for sustained absorption
Bioequivalence studies compare absorption profiles of formulations
Crucial for generic drug development and approval
Ensures therapeutic equivalence between brand-name and generic drugs
Typically involves comparing area under the curve (AUC) and maximum concentration (Cmax )