U01.05.002 Pharmacokinetics

Written by

Pharmacokinetics describes what the body does to the drug, including absorption, distribution, metabolism, and excretion.

Bioavailability (F)

Definition: Fraction of an administered drug that reaches systemic circulation.
IV administration: F = 100%.
Oral administration: F < 100% due to:
- Incomplete absorption
- First-pass metabolism in the liver
Calculation (from plasma concentration vs. time curve):

AUC = Area Under the Curve

Volume of Distribution (Vd)

Definition: Theoretical volume that relates the amount of drug in the body to plasma drug concentration.

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

Influences:
- ↑ Vd in liver/kidney disease (due to ↓ protein binding).
- Drugs may distribute into multiple compartments.
- Hemodialysis is most effective for drugs with low Vd.

Vd by Compartment & Drug Type

Vd Level	Compartment	Drug Types
Low	Intravascular	Large, charged molecules; plasma protein-bound drugs
Medium	Extracellular fluid (ECF)	Small hydrophilic molecules
High	All tissues (incl. fat)	Small lipophilic molecules; tissue protein-bound drugs

Clearance (CL)

Definition: Volume of plasma cleared of drug per unit time.
Equation:

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

(where $K_e$ = elimination constant)

Clinical relevance: Clearance is impaired in cardiac, hepatic, or renal dysfunction.

Half-life (t½)

Definition: Time required to eliminate 50% of the drug from the body.

$elimination)t_{1/2} = \frac{0.7 \times V_d}{CL} \quad \text{(first-order elimination)}$

Number of half-lives and % drug remaining:

# of Half-lives	1	2	3	4
% Remaining	50%	25%	12.5%	6.25%

Key facts:
- Steady state = rate of drug administration = rate of drug elimination.
- In first-order kinetics:
  - 4–5 half-lives → reach steady state.
  - 3.3 half-lives → reach ~90% steady state.

Learning Objective:

Understand and apply the core pharmacokinetic parameters—bioavailability, volume of distribution, clearance, and half-life—to predict drug dosing, steady state, and drug elimination patterns in clinical scenarios.