Pharmacokinetics: From Absorption to Elimination

Pharmacokinetics (PK) describes the journey of a drug through the body, encompassing its absorption, distribution, metabolism, and excretion (ADME). Understanding PK principles is essential for optimizing dosing regimens, minimizing toxicity, and improving therapeutic outcomes.

Absorption

Oral Bioavailability

Bioavailability (F) is the fraction of an administered dose that reaches systemic circulation unchanged.

• First‑pass metabolism in the gut wall and liver can markedly reduce F.

• Factors influencing F: solubility, permeability, formulation, food effects.

• Typical F values: 0.2–0.9 for most oral drugs.

Other Routes

• Intravenous (IV): F = 1 by definition.

• Intramuscular (IM) and subcutaneous (SC): absorption rate depends on vascularity.

• Inhalation, transdermal, rectal: unique absorption kinetics.

Distribution

• Volume of Distribution (Vd): theoretical space into which the drug distributes.

• Plasma Protein Binding: only free drug is pharmacologically active.

• Blood‑to‑Plasma Ratio: indicates tissue penetration.

Metabolism

Phase I and Phase II Reactions

Phase I (oxidation, reduction, hydrolysis) often introduces reactive intermediates; Phase II (conjugation) increases solubility for excretion.

Key Enzymes

• Cytochrome P450 family (CYP3A4, CYP2D6, CYP2C9, etc.)

• UDP‑glucuronosyltransferases (UGTs)

• Transferases (e.g., sulfotransferases)

Excretion

Renal and biliary pathways are the primary routes for drug elimination.

• Renal clearance (Clrenal) depends on glomerular filtration, tubular secretion, and reabsorption.

• Biliary excretion is mediated by transporters such as BCRP and MRP2.

• Half‑life (t½) is a key clinical parameter for dosing intervals.

Key PK Parameters

Practical Clinical Pearls

• Use the Rule of 80 (Css = (F × Dose) / (Cl × τ)) to estimate steady‑state concentration.

• For drugs with narrow therapeutic windows, monitor trough levels and adjust dose based on clearance changes (e.g., renal impairment).

• When prescribing drugs that are CYP inhibitors, anticipate increased plasma levels of co‑administered agents metabolized by the same enzyme.

• Consider age‑related changes: elderly patients often have reduced renal clearance and altered Vd, necessitating dose reductions.

• In pediatric dosing, weight‑based calculations should account for developmental differences in enzyme maturation and renal function.

Remember: Pharmacokinetics is the foundation of rational drug dosing. Accurate interpretation of PK parameters leads to safer, more effective therapy.