U01.05.002 Pharmacokinetics

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Learning Objectives

Master the quantitative principles of Pharmacokinetics. Understand how the body processes drugs through absorption, distribution, metabolism, and excretion (ADME), and learn to calculate key parameters like bioavailability, volume of distribution, and clearance for the USMLE Step 1.

1. Bioavailability (F)

Bioavailability is the fraction of an administered dose that reaches the systemic circulation in an unchanged form.

Route Bioavailability (F) Reasoning
Intravenous (IV) 100% (F = 1) Bypasses absorption and first-pass metabolism.
Oral (PO) < 100% (F < 1) Incomplete absorption and first-pass metabolism (liver).

F = \frac{AUC_{oral} \times Dose_{IV}}{Dose_{oral} \times AUC_{IV}}

2. Volume of Distribution (V_d)

V_d is a theoretical volume that relates the total amount of drug in the body to its plasma concentration. It helps determine the loading dose.

V_d Level Compartment Drug Characteristics
Low Intravascular (Plasma) Large/charged molecules; highly protein-bound.
Medium Extracellular Fluid (ECF) Small, hydrophilic (polar) molecules.
High All tissues (including fat) Small, lipophilic molecules; tissue-bound.

V_d = \frac{\text{Amount of drug in the body}}{\text{Plasma drug concentration}}

3. Clearance ($CL$)

Clearance is the volume of plasma from which a drug is completely removed per unit of time.

Parameter Details
Formula CL = \frac{\text{Rate of elimination}}{\text{Plasma concentration}} = V_d \times K_e
Impairment Occurs with defects in cardiac, hepatic, or renal function.
Dialysis Hemodialysis is most effective for drugs with low V_d.

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4. Half-life (t_{1/2}) and Steady State

The half-life determines how long it takes for a drug to reach a steady state or be eliminated.

Concept Key Values
Steady State Rule Takes 4–5 half-lives to reach steady state (and to be “cleared”).
90% Level Takes 3.3 half-lives to reach 90% of steady state.
Elimination Table 1 t_{1/2} = 50% left; 2 t_{1/2} = 25% left; 3 t_{1/2} = 12.5% left; 4 t_{1/2} = 6.25% left.

t_{1/2} = \frac{0.7 \times V_d}{CL}

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High-Yield Clinical Pearls:

  • Protein Binding: Liver and kidney disease decrease plasma protein (albumin). This increases the free fraction of the drug, effectively increasing the V_d.
  • The t_{1/2} Constant: In first-order kinetics, the half-life is constant regardless of concentration. In zero-order kinetics (e.g., Ethanol), the rate of elimination is constant, but the half-life varies.
  • Loading vs Maintenance: V_d is used to calculate the Loading Dose, whereas CL is used to calculate the Maintenance Dose.

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