Pharmacokinetics forms the scientific backbone of rational drug therapy by explaining how a drug moves through the body over time. From the moment a drug enters systemic circulation until it is eliminated, its concentration changes continuously. Unit 3 focuses on the principles of pharmacokinetics, compartmental and non-compartmental models, different routes of drug administration, and key pharmacokinetic parameters that guide dosage design and clinical decision-making.
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Introduction to Pharmacokinetics
Definition and Scope
Pharmacokinetics is defined as the quantitative study of absorption, distribution, metabolism, and excretion (ADME) of drugs. It answers critical clinical questions such as how fast a drug acts, how long it remains effective, and what dose is required to maintain therapeutic levels without causing toxicity.
Importance in Clinical Practice
Understanding pharmacokinetics helps optimize dosing regimens, predict drug interactions, adjust doses in renal or hepatic impairment, and ensure patient safety. It bridges pharmaceutical science and clinical pharmacology, making it essential for drug development and therapeutic monitoring.
Pharmacokinetic Models: Simplifying Drug Behavior
Compartment Models
Compartment models simplify the body into one or more hypothetical compartments where the drug distributes uniformly.
One-Compartment Open Model
In the one-compartment open model, the body is considered a single, homogeneous unit. After drug administration, the drug distributes instantaneously throughout the compartment, and elimination occurs simultaneously. This model is widely used because of its simplicity and applicability to many drugs.
Non-Compartment Models
Non-compartmental analysis does not assume a specific physiological structure. Instead, it relies on statistical moment theory to calculate parameters such as AUC and clearance. This approach is commonly used in bioavailability and bioequivalence studies.
Physiological Models
Physiological or perfusion-based models describe drug distribution based on actual organ volumes and blood flow rates. These models are complex but provide realistic insights into drug behavior in different tissues.
Routes of Drug Administration and Their Pharmacokinetics
Intravenous Injection (Bolus)
An intravenous bolus injection delivers the drug directly into systemic circulation, producing an immediate peak plasma concentration. Since absorption is bypassed, bioavailability is 100 percent. The decline in drug concentration reflects distribution and elimination processes.
Intravenous Infusion
In intravenous infusion, the drug is administered at a constant rate over time. Plasma concentration gradually rises until it reaches a steady-state level, where the rate of drug input equals the rate of elimination. Infusion is preferred when constant plasma levels are required.
Extravascular Administration
Extravascular routes such as oral, intramuscular, or subcutaneous administration involve an absorption phase. The drug must cross biological membranes before entering circulation, making absorption rate a critical determinant of onset and intensity of action.
Key Pharmacokinetic Parameters and Their Significance
Elimination Rate Constant (KE)
KE represents the fraction of drug eliminated per unit time. It determines how rapidly a drug is removed from the body and directly influences half-life and dosing intervals.
Half-Life (t½)
The half-life is the time required for plasma drug concentration to decrease by 50 percent. It helps determine dosing frequency and the time needed to reach steady state or complete drug elimination.
Volume of Distribution (Vd)
Volume of distribution is a theoretical volume that relates the amount of drug in the body to the plasma concentration. A high Vd indicates extensive tissue distribution, while a low Vd suggests confinement mainly to the bloodstream.
Area Under the Curve (AUC)
AUC represents the total systemic exposure of the body to the drug. It is a crucial parameter for comparing bioavailability and assessing drug absorption across different formulations.
Absorption Rate Constant (Ka)
Ka describes the speed at which a drug is absorbed into systemic circulation following extravascular administration. Faster absorption leads to quicker onset of action.
Total Clearance (Clt)
Clearance is the volume of plasma from which the drug is completely removed per unit time. It reflects the combined effect of renal, hepatic, and other elimination pathways.
Renal Clearance (CLR)
Renal clearance quantifies the contribution of the kidneys to drug elimination. It is particularly important for dose adjustment in patients with renal impairment.
Methods of Drug Elimination
First-Order Elimination
Most drugs follow first-order kinetics, where the rate of elimination is proportional to the drug concentration. This results in a constant fraction of drug being eliminated per unit time.
Zero-Order Elimination
In zero-order kinetics, a constant amount of drug is eliminated per unit time, regardless of concentration. This occurs when elimination pathways become saturated, as seen with drugs like phenytoin and ethanol.
Clinical Applications of Pharmacokinetic Parameters
Dose Optimization
Pharmacokinetic parameters help calculate loading and maintenance doses to achieve and maintain therapeutic plasma levels.
Therapeutic Drug Monitoring
Drugs with narrow therapeutic indices require monitoring of plasma concentrations. Pharmacokinetic principles guide interpretation and dose adjustments.
Special Populations
Age, disease state, pregnancy, and organ dysfunction can alter pharmacokinetics. Understanding these changes ensures individualized and safe drug therapy.