Key concepts in immunopharmacology, oncology and toxicology

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Drug Elimination Kinetics and Monitoring

The relationship between the administered dose and metabolic clearance is described mathematically. While most drugs follow first-order kinetics at therapeutic doses, overdose situations saturate cellular enzyme systems, transitioning to zero-order kinetics.

📉 First Order Kinetics

The rate of elimination is directly proportional to the plasma concentration of the drug (C).

• The elimination half-life (t_1/2) remains constant, independent of the dose: t_1/2 = (0.693 · V_d)/(Cl)
• A constant fraction of the drug is eliminated per unit of time.
• Clearance (Cl) remains constant throughout the dosing interval.

📊 Zero Order Kinetics

The elimination rate is constant and independent of the drug concentration.

• Saturation of transport or molecular metabolization mechanisms (e.g. alcohol dehydrogenase, phenytoin at high doses, salicylates in overdose).
• A constant amount of drug is eliminated per unit of time: -(dC)/(dt) = K₀
• The elimination half-life increases as the plasma concentration rises.

Dynamics of metabolic saturation

In toxicological management, the transition from first-order to zero-order kinetics is described by the Michaelis-Menten equation: ν = V_max · CK_m + C When plasma concentrations of the xenobiotic (C) far exceed the affinity constant of the enzyme (K_m), the elimination rate approaches V_max, making clearance independent of the circulating concentration. This drastically prolongs the patient's exposure to deleterious effects, justifying active intervention with antidotes or extracorporeal purification techniques.