What is pharmacokinetics?

Pharmacokinetics: The Study of How the Body Processes Drugs

Pharmacokinetics is the study of what the body does to a drug, encompassing the processes of absorption, distribution, metabolism, and excretion (ADME) of medications after administration. 1 This fundamental concept is essential for understanding drug behavior in the body and optimizing therapeutic outcomes.

Core Principles of Pharmacokinetics

Definition and Scope

• Pharmacokinetics describes how the body handles drugs, in contrast to pharmacodynamics which describes what drugs do to the body 1, 2
• Pharmacokinetic information is required to optimize pharmacodynamic responses 2
• The study of pharmacokinetics involves tracking the time course of drug concentrations in the body 3

The ADME Processes

1. Absorption

• Refers to how drugs enter the bloodstream from the site of administration
• Bioavailability is a key parameter measuring the fraction of an administered dose that reaches systemic circulation 1
• Can be affected by food, as seen with metformin where food decreases absorption extent and slightly delays absorption 4

2. Distribution

• Describes how drugs move throughout the body after entering the bloodstream
• Volume of distribution (V/F) is a primary parameter that may vary with physiologic and pathologic conditions 2
• Protein binding affects drug distribution and can influence pharmacokinetic parameters 2
  • Example: Metformin is negligibly bound to plasma proteins and has an apparent volume of distribution of 654 ± 358 L 4

3. Metabolism

• Primarily occurs in the liver through cytochrome P450 (CYP) enzymes
• CYP3A4 is responsible for metabolizing more than 50% of all drugs 5
• Some drugs (like metformin) may not undergo significant metabolism and are excreted unchanged 4

4. Excretion

• Primarily occurs through the kidneys (renal clearance) and/or biliary system
• Clearance is a primary pharmacokinetic parameter that allows clinicians to prescribe correct dosage regimens 2
• Example: Metformin is primarily eliminated via renal clearance, with approximately 90% eliminated via this route within 24 hours 4

Key Pharmacokinetic Parameters

Bioavailability

• Measures the fraction of administered drug that reaches systemic circulation 1
• Varies by route of administration and drug formulation
• Example: Metformin tablets have approximately 50-60% bioavailability under fasting conditions 4

Volume of Distribution

• Relates the amount of drug in the body to the concentration in the blood or plasma
• Larger volumes indicate greater distribution into tissues
• Can be affected by disease states like congestive heart failure, which typically reduces volume of distribution 6

Clearance

• Measures the body's ability to eliminate a drug
• Primary pharmacokinetic disposition parameter 2
• Includes hepatic, renal, and other routes of elimination
• May be impaired in disease states, leading to higher drug concentrations 6

Half-life

• Time required for drug concentration to decrease by 50%
• Composite parameter reflecting both clearance and volume of distribution 2
• Determines dosing intervals and time to reach steady state
• Example: Metformin has a plasma elimination half-life of approximately 6.2 hours 4

Clinical Applications of Pharmacokinetics

Drug-Drug Interactions

• Pharmacokinetic interactions occur when one drug influences the ADME processes of another drug 5
• Can result from altered absorption, distribution, metabolism, or excretion 5
• CYP450 enzyme inhibition or induction is a common mechanism for drug interactions 5
• Clinical consequences depend on the pharmacological and toxic effects of both parent drug and metabolites 5

Special Populations

• Pharmacokinetic parameters can be altered in:
  • Elderly patients (reduced clearance, prolonged half-life) 4
  • Patients with renal impairment (prolonged half-life, decreased clearance) 4
  • Patients with hepatic impairment
  • Patients with heart failure (reduced volume of distribution, impaired clearance) 6

Therapeutic Drug Monitoring

• Uses pharmacokinetic principles to optimize dosing
• Particularly important for drugs with narrow therapeutic windows
• Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) are in vitro tests that help determine antimicrobial dosing 5

Pharmacokinetics vs. Pharmacodynamics

• Pharmacokinetics: What the body does to the drug (ADME processes) 1
• Pharmacodynamics: What the drug does to the body (drug effects) 1
• Pharmacodynamics describes the relationship between drug concentration and pharmacologic effect 5
• The integration of both provides more clinically relevant relationships for optimizing drug therapy 5

Common Pitfalls in Pharmacokinetic Assessment

• Failing to account for patient-specific factors (age, disease states, genetics)
• Overlooking potential drug-drug interactions
• Not considering the impact of food on drug absorption
• Assuming linear pharmacokinetics for all drugs at all doses
• Neglecting the importance of protein binding changes in disease states

Understanding pharmacokinetics is essential for appropriate drug selection, dosing, and monitoring to optimize therapeutic outcomes while minimizing adverse effects.