Pharmacology Chapter on Drug Absorption

Biopharmaceutics and Drug Absorption

• Biopharmaceutics examines the interplay of drug properties, dosage forms, and routes of administration on systemic drug absorption.
• Learning objectives include describing cell membrane characteristics, mechanisms for absorption, transporters involved, pH influence, physiological factors, first-pass effect, enterohepatic cycling, and the impact of food/disease on absorption. Strategies for enhancing oral drug absorption are also considered.

Cell Membrane Structure and Mechanisms

• Biological membranes act as barriers to drug delivery.
• Transcellular absorption involves movement across cells, often through lipophilic molecules.
• Paracellular absorption occurs between cells, generally via small hydrophilic molecules.
• Some drugs use both mechanisms
• The fluid mosaic model describes the cell membrane's structure, with proteins embedded in a lipid bilayer.

Passive Diffusion

• Molecules move from higher to lower concentrations.
• No energy is expended.
• An important mechanism for many drugs.
• Directly related to temperature.
• Inversely related to molecular size.
• Affected by Fick's Law (rate of diffusion): dQ/dt = DAK (C_GI - C_p)/h .
• Factors impacting passive diffusion include the concentration gradient (driving force), the partition coefficient (lipid solubility), the surface area of the membrane, and membrane thickness.

Active Transport

• Transport against the concentration gradient
• Energy-consuming.
• Important process for drug absorption and secretion
• Carrier protein are highly selective for the drug (structure-specific)
• Saturable at high concentration of drug(amount of carrier )
• Affected by competitive inhibition from similar substances

Membrane Transport Proteins

• Carrier and channel proteins are important for drug absorption in the intestines, liver, kidneys, and brain.
• Influx transporters increase drug absorption, while efflux transporters decrease it.
• Specific examples of carriers like OATP2, OATP6, OCT1 (and substrates) are crucial.
• ATP-binding cassette (ABC) transporters (eg., P-glycoprotein) play critical roles in drug multidrug resistance.

Weak Electrolytes and pH

• Most drugs are weak acids or bases existing in ionized and non-ionized forms.
• Ionization is affected by pH and pKa.
• Non-ionized forms are lipophilic and more easily absorbed. The ionized forms are more water soluble.
• The Henderson-Hasselbalch equation describes the relationship between pH and pKa.

pH-partition Hypothesis

• Differences in pH across a membrane influence drug ionization and absorption. Ionized forms are generally less absorbed than non-ionized forms. The compartment with higher ionization will contain a higher concentration of the total amount.

Effect of Food on Drug Absorption

• Food can affect drug absorption by altering pH, motility, and the enzyme activity.
• Food reduces certain drug absorption but increase the absorption of some basic drugs.
• Some drugs are best taken with food (e.g., lipophilic substances).
• Other drugs may be harmful taken with food (e.g., antibiotics).

First-pass Effect

• Elimination of drug by the liver or gut during the first pass through the systemic circulation.
• Can significantly decrease the bioavailability of the drug.
• First-pass effect can reduce or eliminate the drug's systemic effectiveness.

Enterohepatic Circulation

• Drug absorption, secretion into bile, storage in gallbladder, re-absorption from intestine and returning to circulation.
• This cycle can prolong drug exposure times and may increase the amount of drug in the body.

Double Peak Phenomenon

• Some drugs exhibit a double-peaked plasma concentration curve after a single dose.
• This is often due to differences in gastric emptying, drug dissolution, and enterohepatic circulation.

Effect of Disease on GI Drug Absorption

• Disease-related conditions such as CHF, Parkinson's, and Celiac disease can affect drug absorption.
• Altered blood flow, GI motility, and permeability or gastric pH can change the amount of drug absorbed.

Effect of Drugs on GI Drug Absorption

• Drugs (e.g., antacids, anticholinergics, antidepressants) affect GI tract functions, which alter drug absorption.

Effect of Nutrients on GI Drug Absorption

• Nutrients can impact drug absorption, specifically relevant to calcium, dietary fiber, grapefruit juice, and others.

General Important Info

• Bioavailability is the fraction of administered drug reaching the systemic circulation, and this is frequently impacted by the properties of the drug and physiological factors.
• This is an overview, and specific situations and drug entities need to be considered for detailed information and specific recommendations.

Colonic Drug Delivery

• Some drugs are optimized for colonic delivery. This is useful if they are broken down in the stomach and small intestine.
• Drugs formulated and optimized for colonic absorption might be effective treating local symptoms in the large intestine area.

Drug Absorption and Transport Mechanisms

• Absorption of a drug can happen by various mechanisms, passive diffusion and/or active transport. Knowing the specific delivery method is helpful in determining when a drug is delivered to the target.

Important Considerations

• Many factors influence drug absorption in the gastrointestinal (GI) tract.
• Appropriate consideration of these factors is essential for optimal therapeutic outcomes and to avoid negative side effects.

Test your knowledge on key concepts related to drug absorption in this pharmacology quiz. Explore factors influencing drug bioavailability, mechanisms of absorption, and the effects of gastric emptying. Understand the significance of the double peak phenomenon in drug kinetics.