Drug Administration

Core Principles of Pharmacokinetics:

Drug Absorption:

• Absorption is the transfer of a drug from its site of administration to the site of measurement.

  • The site of measurement is usually the blood plasma.

  • Absorption determines how quickly and how much drug enters the systemic circulation.

Drug Distribution:

• Distribution is the reversible transfer of a drug between the blood and body tissues.

  • Drugs may distribute into organs, fat, muscle, or bind to plasma proteins.

  • Distribution influences the concentration of drug at the target site.

Drug Elimination:

• Elimination is the irreversible removal of a drug from the body.

  • It occurs through metabolism or excretion.

  • Metabolism commonly occurs in the liver.

  • Excretion commonly occurs via the kidneys.

Plasma Drug Concentration:

• Plasma drug concentration is a central principle in pharmacology.

  • The magnitude of a drug’s effect is related to the amount of drug at its target.

  • Most drugs reach their targets via the bloodstream.

• Plasma concentration is often used as a surrogate for target concentration.

  • Blood and urine samples are usually the only accessible measurements.

  • There is often a good correlation between plasma concentration and therapeutic effect.

Plasma Concentration Versus Time Curve:

• A concentration versus time curve shows how plasma drug levels change after administration.

  • Immediately after oral administration, plasma concentration is driven mainly by absorption.

    • As absorption continues, elimination also increases.

      • At C_max and T_max, the rate of absorption equals the rate of elimination.

        • After this point, elimination exceeds absorption and plasma concentration falls.

          • In the terminal phase, plasma concentration is influenced only by elimination.

• The concentration versus time profile allows identification of:

  • Absorption phase.

  • Distribution phase.

  • Elimination phase.

Therapeutic Window and Therapeutic Index:

The therapeutic window is the range of plasma drug concentrations that produce therapeutic effects without unacceptable toxicity.

• The minimum efficacious concentration is the lowest concentration that produces a therapeutic effect.

• The maximal tolerated concentration is the highest concentration that can be tolerated without toxic effects.

• The therapeutic window lies between the minimum efficacious concentration and the maximal tolerated concentration.

  • Concentrations below this range are ineffective.

  • Concentrations above this range cause adverse effects.

Drugs With a Narrow Therapeutic Window:

• Drugs with a narrow therapeutic window are difficult to use safely.

  • Small changes in dose can lead to toxicity or treatment failure.

  • Patients often require regular monitoring.

• The relationship between plasma concentration and effect may not hold if:

  • The effect is mediated by an active metabolite.

  • The effect is irreversible.

  • Drug kinetics differ between plasma and the target tissue.

Influence of Absorption, Distribution, and Elimination:

Absorption:

• Unless administered intravenously, absorption introduces a delay before the drug appears in plasma.

  • This delay affects the onset of drug action.
    

Distribution and Elimination:

• Distribution and elimination reduce plasma drug concentration over time.

  • Metabolism and excretion remove drug from the circulation.

  • These processes determine the duration of action.

Considerations When Choosing a Route of Administration:

• Ease of administration.

  • Patient compliance and ability.

  • Requirement for healthcare professionals or sterile conditions.

• Pharmacokinetic properties of the drug.

  • Speed of onset.

  • Duration of action.

  • Access to the site of action.

• Local versus systemic effects.

• Avoidance of the gastrointestinal tract or liver.

  • Parenteral routes bypass first-pass metabolism.

  • Enteral routes involve the gastrointestinal tract.

• Physicochemical properties of the drug.

  • Volatile drugs may be suitable for inhalation.

• Side effect profile and safety.

Impact of Route of Administration on Pharmacokinetics:

• Different routes of administration produce different plasma concentration profiles.

  • Intravenous administration produces immediate systemic exposure.

  • Intramuscular administration produces slower onset.

  • Oral administration produces the slowest onset and variable absorption.

• Route affects:

  • Time to reach minimum efficacious concentration.

  • Peak plasma concentration.

  • Duration of therapeutic effect.