Advanced BPPK Notes
Chapter: Plasma Drug Concentration–Time Profile and Rates, Rate Constants & Orders of
Reaction
1. Plasma Drug Concentration–Time Profile
Whenever a drug is administered, it undergoes absorption, distribution, metabolism and
excretion (ADME). The plasma drug concentration–time profile is obtained by plotting
plasma concentration against time and represents the overall fate of a drug in the body.
The profile is important because it helps determine Cmax, Tmax, AUC, half-life, clearance,
volume of distribution, bioavailability and therapeutic window.
Absorption phase: During this phase, the rate of absorption exceeds the rate of elimination
and plasma concentration rises.
Peak concentration phase: The maximum plasma concentration (Cmax) occurs at Tmax. At
this point, rate of absorption equals rate of elimination.
Elimination phase: Drug concentration declines because elimination becomes greater than
absorption. This phase is used to estimate half-life and elimination rate constant.
Minimum Effective Concentration (MEC) is the minimum concentration required for
therapeutic action, while Minimum Toxic Concentration (MTC) is the concentration above
which toxicity occurs. The range between them is called the therapeutic window.
Area Under the Curve (AUC) represents total systemic exposure to the drug and is directly
proportional to the extent of absorption.
2. Rates, Rate Constants and Orders of Reaction
A rate process is any process that occurs with time. In pharmacokinetics, absorption,
distribution, metabolism and excretion are all rate processes.
Rate is defined as the change in drug concentration or amount per unit time. The rate
constant (k) is the proportionality constant that relates rate to concentration.
Order of reaction describes how the rate depends on concentration. Pharmacokinetic
processes commonly follow zero-order, first-order or mixed-order kinetics.
Zero-order kinetics: A constant amount of drug is eliminated per unit time irrespective of
concentration. Examples include ethanol and high-dose phenytoin.
Characteristics of zero-order kinetics include concentration-independent elimination,
saturation of elimination pathways and a non-constant half-life.
First-order kinetics: The rate of elimination is directly proportional to drug concentration. A
constant fraction of drug is eliminated per unit time. Most drugs follow first-order kinetics.
Characteristics of first-order kinetics include exponential decline in concentration, constant
half-life and predictable pharmacokinetic behavior.
Mixed-order (capacity-limited) kinetics occurs when a drug follows first-order kinetics at
low concentrations and zero-order kinetics at high concentrations due to enzyme
saturation.
Understanding reaction order is essential for dosage regimen design, prediction of
accumulation, therapeutic drug monitoring and prevention of toxicity.
Quick Revision
Cmax = Maximum concentration; Tmax = Time to reach Cmax; AUC = Extent of drug
exposure; MEC = Minimum effective concentration; MTC = Minimum toxic concentration;
First-order kinetics = constant fraction eliminated; Zero-order kinetics = constant amount
eliminated.