PHARMACOKINETICS

1. What is Pharmacokinetics?

Pharmacokinetics is the study of how a drug moves through the body, often described as "what the body does to the drug." It involves four main processes (ADME): absorption, distribution, metabolism, and excretion, which determine the drug’s onset, duration, and intensity of action.

2. Absorption

Absorption is how a drug moves from its site of administration into the bloodstream. For a drug to be effective, it must first be absorbed (except for IV drugs, which enter directly).

Factors Affecting Absorption:

  • Route of Administration: IV drugs have 100% absorption, while oral drugs may lose some effectiveness due to digestion.

  • Drug Formulation: Tablets, capsules, or solutions may absorb at different rates.

  • Lipid Solubility: Drugs that dissolve in fats are absorbed faster, as they easily pass through cell membranes.

  • Blood Flow to Absorption Site: Better blood flow (like in muscles) increases absorption.

  • Gastrointestinal (GI) Health: Conditions like diarrhea or changes in stomach pH can alter absorption.

3. Routes of Drug Administration

Routes of drug administration impact both the onset and amount of drug absorbed.

  • Oral: Common, but subject to the first-pass effect (metabolism by the liver before entering circulation).

  • Intravenous (IV): Directly enters bloodstream; 100% bioavailability.

  • Intramuscular (IM): Absorbed from muscle; good for slower, sustained release.

  • Subcutaneous (SC): Absorbed from under the skin; slower than IV and IM.

  • Inhalation: Rapid absorption via lungs; ideal for respiratory drugs.

  • Topical/Transdermal: Absorbed through the skin; good for localized or long-acting effects.

4. Distribution

Distribution is the movement of a drug from the bloodstream to various tissues and organs in the body.

Factors Affecting Distribution:

  • Blood Flow to Tissues: Well-perfused organs like the liver, kidneys, and brain receive drugs faster.

  • Lipid Solubility: Lipid-soluble drugs cross cell membranes and the blood-brain barrier more easily.

  • Plasma Protein Binding: Drugs that bind to proteins like albumin stay in the bloodstream longer and are less available to tissues.

  • Tissue Binding: Drugs may accumulate in specific tissues (like fat or bone), prolonging their effects.

5. Metabolism

Metabolism (or biotransformation) is the process by which the body chemically modifies the drug, usually in the liver. This step often transforms drugs into more water-soluble compounds for easier elimination.

Factors Affecting Metabolism:

  • Genetics: Different genetic makeups affect enzyme activity (like CYP450 enzymes).

  • Age: Newborns and elderly patients metabolize drugs more slowly.

  • Liver Health: Conditions like liver disease can reduce drug metabolism.

  • Other Drugs: Some drugs induce or inhibit liver enzymes, affecting the metabolism of other drugs.

  • Diet and Environment: Certain foods (like grapefruit) and habits (like smoking) can affect metabolism.

6. Elimination (Excretion)

Elimination is how the drug leaves the body, primarily through the kidneys (urine), but also through bile, lungs, sweat, and other routes.

Factors Affecting Elimination:

  • Kidney Function: Healthy kidneys are essential for effective drug elimination.

  • Age: Children and elderly patients have altered kidney function.

  • Urine pH: Some drugs are eliminated more easily in certain pH levels.

  • Drug Interactions: Certain drugs can affect kidney function or alter the pH of urine, impacting drug elimination.

7. How Do We Measure ADME Processes?

  • Blood Concentration Levels: Measure how much drug is in the blood at various times to understand absorption and elimination rates.

  • Half-Life: The time it takes for half the drug to be eliminated; helps determine dosing schedules.

  • Clearance Rate: Measures the body’s efficiency in eliminating the drug, often in terms of volume per unit of time (e.g., mL/min).

  • Bioavailability: The fraction of the drug that reaches the bloodstream in an active form (100% for IV, less for oral due to first-pass metabolism).

8. Pharmacokinetic Compartment Model

The compartment model simplifies how drugs move within the body.

  • One-Compartment Model: Assumes the drug distributes instantly and evenly in the body.

  • Two-Compartment Model: Divides the body into central (blood and organs) and peripheral (fat and muscle) compartments. The drug first distributes to the central compartment and then gradually to the peripheral.

These models help in predicting drug concentrations at various times and are useful for understanding dosing, onset, and duration of effects.