Pharmacokinetics: Drug Absorption and Routes

Pharmacokinetic (Absorption)

• Absorption is the movement of a drug from its administration site to the systemic circulation.
• The systemic circulation is the blood circulation throughout the body.
• The site of administration can be oral, intravenous, intramuscular, subcutaneous, etc.
• The bioavailability of a drug refers to the fraction of the administered dose that reaches the systemic circulation.
• Biological membranes are composed of phospholipids, proteins, and carbohydrates.
• Drugs cross biological membranes by various mechanisms, including passive diffusion (driven by the concentration gradient), active transport (requires energy), and facilitated diffusion (requires a carrier protein).

Routes of Administration

• Enteral administration: involves the gastrointestinal tract.
• Oral: Most common, convenient, and economical. Examples include tablets, capsules, and syrups.
• Rectal: Useful for patients who cannot swallow due to nausea, vomiting, or unconsciousness.
• Sublingual: Medication is placed under the tongue for absorption.
• Parenteral administration: administration bypasses the GI tract.
• Intravenous (IV): Directly into the bloodstream, bypassing absorption.
• Intramuscular (IM): Injected into a muscle.
• Subcutaneous (SC): Injected beneath the skin.
• Intradermal: Injected into the skin.
• Intrathecal: Injected into the cerebrospinal fluid.

Pharmacokinetic Parameters

• AUC (Area Under the Curve): Represents the total drug exposure over time. An important parameter for both pharmacokinetic and pharmacodynamic analyses.
• MEC (Minimum Effective Concentration): The lowest concentration of a drug in the bloodstream required for a therapeutic effect.
• Onset: The time taken from drug administration to the first appearance of its pharmacological effect.
• Duration: The time between the appearance of the drug's pharmacological effect and its disappearance, also known as the time between two MECs.
• Cmax: The maximum concentration of the drug in plasma.
• Tmax: The time taken to reach Cmax.
• MTC (Minimum Toxic Concentration): The lowest concentration of a drug that produces toxic effects.

Factors Affecting Oral Absorption

• Gastrointestinal Motility and Emptying: Increased GI motility can lead to reduced absorption.
• Food: Can decrease the absorption of many drugs. For example, tetracycline's absorption is reduced in the presence of calcium.
• Intestinal Blood Flow (Splanchnic Blood Flow): Reduced blood flow can decrease drug absorption.
• Particle Size: Smaller particle size allows for faster and increased absorption.
• Chemical Interactions: Drugs can interact with food or other drugs, affecting pH and dissociation, thereby impacting absorption.

First Pass Metabolism (Enterohepatic Circulation)

• After absorption from the upper gastrointestinal tract, drugs enter the portal circulation.
• The portal vein carries the drug-containing blood to the liver, where it may undergo metabolism before reaching systemic circulation.
• This first-pass metabolism can reduce the bioavailability of orally administered drugs.

Bioavailability of IV Preparations

• IV preparations bypass absorption and directly enter the systemic circulation.
• Therefore, their bioavailability is 100%.