3.2 Drug absorption and factors affecting absorption
4 min read•august 16, 2024
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 , , , and , 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 . Understanding these factors is essential for optimizing drug delivery and predicting drug behavior in the body.
Drug Absorption Mechanisms
Passive and Facilitated Diffusion
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- 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
- 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
- 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 time (delayed with high-fat meals)
- May change pH or directly interact with drug
- Example: tetracyclines chelate with calcium in dairy products
- in liver reduces oral drug
- 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
- actively move drugs into cells
- Enhance absorption of certain compounds
- Examples: (OATPs), peptide transporters
- OATP1B1 involved in statin uptake in liver
- pump drugs out of cells
- Can limit absorption and contribute to drug resistance
- (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
Transporter-Mediated Interactions and 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
Drug Formulation & Absorption
Pharmaceutical Forms and Release Mechanisms
- Pharmaceutical form significantly influences dissolution and absorption
- , 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
- used to enhance absorption of poorly soluble drugs (griseofulvin)
Novel Delivery Systems and Bioequivalence
- Excipients impact absorption by altering drug properties
- Can change , stability, or membrane interaction
- Example: cyclodextrins enhancing solubility of lipophilic drugs
- Novel drug delivery systems enhance absorption
- 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 ()
Key Terms to Review (27)
Active Transport: Active transport is the process by which cells move molecules across their membranes against a concentration gradient, using energy typically derived from ATP. This mechanism is essential for maintaining cellular homeostasis, as it enables cells to take in necessary nutrients and expel waste products despite unfavorable concentration gradients. The importance of active transport extends to how drugs are absorbed into the body and distributed, influencing their bioavailability and effectiveness.
Bioavailability: Bioavailability refers to the proportion of a drug that enters the systemic circulation when introduced into the body and is available for therapeutic effect. It is influenced by factors such as the route of administration, formulation of the drug, and individual patient characteristics, making it a crucial aspect of pharmacology, drug development, and therapeutic effectiveness.
Clinical Pharmacokinetics: Clinical pharmacokinetics is the study of how drugs are absorbed, distributed, metabolized, and excreted in the body, specifically focusing on optimizing drug therapy in individual patients. It aims to understand the relationship between drug concentration in the body and therapeutic outcomes to enhance efficacy while minimizing toxicity. By considering factors such as patient characteristics and clinical conditions, clinical pharmacokinetics plays a vital role in personalizing medication regimens and ensuring safe and effective treatment.
Cmax: Cmax refers to the maximum concentration of a drug in the bloodstream after it has been administered. This key pharmacokinetic parameter is crucial for understanding how drugs behave in the body, including their absorption, distribution, metabolism, and elimination. Cmax provides insight into the peak efficacy of a drug, as well as potential toxicity when concentrations exceed safe levels.
Efflux Transporters: Efflux transporters are proteins that facilitate the movement of drugs and other substances out of cells, playing a crucial role in pharmacokinetics and drug absorption. These transporters can significantly influence the bioavailability of medications by controlling how much of a drug remains in the body after administration. By actively pumping substances out, efflux transporters can also help protect cells from potential toxins and maintain homeostasis.
Endocytosis: Endocytosis is a cellular process in which substances are brought into the cell by engulfing them in a membrane-bound vesicle. This mechanism plays a crucial role in drug absorption, as it allows larger molecules, including certain drugs, to be transported across cellular membranes, which is essential for their effectiveness.
Facilitated Diffusion: Facilitated diffusion is a process that allows substances to cross membranes with the assistance of special proteins called transport proteins. This method of transport is essential for the absorption of various drugs into the bloodstream, as it enables larger or polar molecules to pass through the lipid bilayer of cell membranes without expending energy. Facilitated diffusion plays a crucial role in determining how effectively a drug is absorbed in the body, influencing factors such as bioavailability and therapeutic effectiveness.
First-pass metabolism: First-pass metabolism refers to the process by which a drug is metabolized in the liver before it reaches systemic circulation. This metabolic process significantly affects the bioavailability of orally administered drugs, as a substantial portion can be transformed into inactive metabolites or reduced in concentration, impacting their overall effectiveness and therapeutic outcomes.
Formulation: Formulation refers to the process of combining various ingredients and excipients to create a specific dosage form of a drug that can be effectively delivered to patients. This process is crucial because it influences how a drug is absorbed, distributed, metabolized, and eliminated in the body. Proper formulation ensures the stability, efficacy, and safety of the medication while considering factors like bioavailability and patient compliance.
Gastric Emptying: Gastric emptying refers to the process by which the contents of the stomach are moved into the small intestine for further digestion and absorption. This process is crucial because it influences how quickly and effectively drugs and nutrients enter the bloodstream. Factors such as food composition, gastric motility, and hormonal signals play significant roles in regulating the rate of gastric emptying.
In Vitro Studies: In vitro studies refer to experiments conducted in a controlled environment outside of a living organism, often using cells, tissues, or biological molecules in lab settings. These studies are crucial for understanding drug interactions, biological mechanisms, and toxicity without the complexities and ethical concerns associated with in vivo studies. They provide valuable preliminary data in the early stages of drug development and are essential for assessing how drugs will be absorbed in the body.
Influx Transporters: Influx transporters are specialized proteins located in cell membranes that facilitate the movement of specific substances, such as drugs and nutrients, into cells. They play a crucial role in drug absorption by enabling the uptake of molecules from the extracellular environment, which significantly impacts how effectively a drug reaches its target site within the body.
Injections: Injections are a method of delivering medication directly into the body using a syringe and needle. This route of administration allows for quick absorption of drugs into the bloodstream, bypassing the digestive system, which can significantly affect how fast and effectively a drug works. Injections can be categorized into several types, including intramuscular, subcutaneous, and intravenous, each with distinct absorption rates and clinical applications.
Lipid Bilayer: The lipid bilayer is a fundamental structural component of cell membranes, composed of two layers of phospholipids arranged tail-to-tail. This arrangement creates a semi-permeable barrier that separates the internal environment of the cell from the external surroundings, allowing for selective transport of substances and maintaining homeostasis. The lipid bilayer's fluid nature enables flexibility and the movement of proteins within the membrane, which plays a critical role in drug absorption and the overall functionality of cells.
Liposomal Delivery Systems: Liposomal delivery systems are nanoscale carriers composed of lipid bilayers that encapsulate drugs, enhancing their solubility, stability, and bioavailability. These systems are designed to improve drug absorption by facilitating the transport of hydrophobic compounds through biological barriers, ultimately leading to increased therapeutic effectiveness and reduced side effects.
Membrane permeability: Membrane permeability refers to the ability of substances to pass through a biological membrane, which is critical for the transport of drugs and nutrients into and out of cells. This property is influenced by factors such as the lipid composition of the membrane, the size and charge of the molecules, and the presence of transport proteins. Understanding membrane permeability is essential for grasping how drugs are absorbed into the bloodstream and how they are distributed throughout the body.
Micronization: Micronization is a process that reduces the particle size of a substance to the micrometer scale, typically between 1 to 100 microns. This technique enhances drug absorption by increasing the surface area of the drug, leading to improved solubility and bioavailability, which are crucial factors for effective pharmacological action in the body.
Nanoparticles: Nanoparticles are tiny particles that range in size from 1 to 100 nanometers. Due to their small size, they exhibit unique physical and chemical properties, which can enhance drug delivery and absorption, making them a valuable tool in pharmacology and medicine. Their large surface area to volume ratio allows for increased interaction with biological systems, facilitating improved solubility, stability, and bioavailability of drugs.
Organic Anion Transporting Polypeptides: Organic anion transporting polypeptides (OATPs) are a family of membrane transport proteins that facilitate the uptake of various organic anions, including drugs and endogenous compounds, into cells. These proteins play a critical role in drug absorption by influencing how well drugs are taken up in various tissues, especially in the liver and intestines, which are key sites for drug metabolism and distribution.
P-glycoprotein: P-glycoprotein is a membrane transporter protein that plays a crucial role in the absorption, distribution, and elimination of various drugs. It functions by actively pumping certain drugs and xenobiotics out of cells, particularly in tissues like the intestines, liver, and blood-brain barrier, impacting how effectively medications can enter systemic circulation. Understanding p-glycoprotein is essential because it influences drug bioavailability and can lead to drug interactions or resistance.
Passive diffusion: Passive diffusion is the process by which substances move across cell membranes from an area of higher concentration to an area of lower concentration without the need for energy input. This movement relies on the concentration gradient and is crucial in determining how drugs are absorbed into the bloodstream and distributed throughout the body, impacting overall drug efficacy and safety.
PH level: The pH level is a measure of how acidic or basic a solution is, on a scale of 0 to 14, with 7 being neutral. In the context of drug absorption, pH levels are crucial because they influence the solubility and permeability of drugs in biological systems, ultimately affecting how well and how quickly a drug is absorbed into the bloodstream.
Solubility: Solubility is the property of a substance to dissolve in a solvent, forming a homogeneous solution. This characteristic is essential in pharmacology because it influences how well a drug can be absorbed into the bloodstream after administration. Factors such as temperature, pH, and the nature of both the solute (the drug) and solvent (usually water or lipid-based) play a critical role in determining solubility, affecting overall drug efficacy and bioavailability.
Surface Area: Surface area refers to the total area that the surface of an object occupies. In pharmacology, it plays a critical role in determining how effectively a drug is absorbed into the bloodstream, as larger surface areas allow for greater absorption of drugs. Factors such as the formulation of the drug and the route of administration can significantly influence the surface area available for absorption.
Tablets: Tablets are solid dosage forms of medication that are created by compressing powders or granules into a specific shape, often circular or oval. They can be designed to dissolve quickly for rapid absorption or formulated for delayed or extended release, making them versatile in terms of how the drug is delivered into the body and absorbed into the bloodstream.
Tmax: tmax refers to the time taken for a drug to reach its maximum concentration in the bloodstream after administration. This is an essential pharmacokinetic parameter, as it helps in understanding the absorption rate of a drug and influences its onset of action and overall effectiveness. The value of tmax can vary based on numerous factors such as the drug formulation, route of administration, and individual patient characteristics.
Transporters: Transporters are specialized proteins found in cell membranes that facilitate the movement of substances across the cell membrane. They play a critical role in drug absorption by allowing drugs to enter cells, thus influencing the bioavailability and therapeutic effects of medications. By mediating the transport of various molecules, transporters can significantly impact how drugs are absorbed in different tissues, which is essential for their pharmacological action.