Pharmacokinetics

Definition

Pharmacokinetics is the branch of pharmacology that studies the movement of drugs within the body. It involves the processes of absorption, distribution, metabolism (biotransformation), and excretion—often summarized by the acronym ADME. Pharmacokinetics explains how the body affects a drug after administration and determines the onset, duration, and intensity of a drug’s effect.

First-Order Kinetics

Definition

In first-order kinetics, the rate of drug elimination is directly proportional to the drug’s concentration in the plasma, meaning a constant percentage of the drug is eliminated per unit of time. Most drugs follow this pattern, as metabolic enzymes are not saturated at therapeutic levels.

Characteristics

  • The rate of elimination depends on the drug concentration.
  • Half-life (t½) remains constant, regardless of concentration.
  • Elimination follows an exponential decrease, with the concentration reducing by half during each half-life period.

Example Drugs

  • Paracetamol (acetaminophen)
  • Ibuprofen
  • Aspirin (at low doses)

Clinical Significance

First-order kinetics offers predictability, simplifying dosing schedules and maintaining steady therapeutic levels.

Zero-Order Kinetics

Definition

In zero-order kinetics, the rate of drug elimination is independent of the plasma concentration, with a constant amount eliminated per time unit. This occurs when metabolic pathways become saturated, often at high or toxic doses.

Difference between First-Order and Zero-Order Kinetics

Characteristics

  • The elimination rate remains constant, independent of drug concentration.
  • There is no fixed half-life since elimination is constant.
  • Commonly seen at high doses where elimination pathways are saturated.

Example Drugs

  • Phenytoin (anticonvulsant)
  • Aspirin (at high/toxic doses)
  • Ethanol (alcohol)

Clinical Significance

Drugs exhibiting zero-order kinetics at high doses can accumulate, posing a toxicity risk. Dosing requires careful adjustment, as small increases can significantly raise plasma levels. Blood level monitoring is essential to prevent toxicity.