Bobbala_814_1 Basic PK

West Virginia University

• School of Pharmacy

• Basic Pharmacokinetics

• Instructor: Sharan Bobbala, Ph.D.

Overview

• Definition of pharmacokinetics and applications

• Pharmacokinetic models

• Volume of distribution

• Clearance

• First-order and zero-order elimination

Objectives

• Define and differentiate between pharmacokinetics and clinical pharmacokinetics.

• Describe the concept of therapeutic concentration range.

• Explain one- and two-compartment models with clinical examples.

• Define apparent volume of distribution; calculate using mathematical equations.

• Define drug clearance.

• Describe first-order vs. zero-order elimination.

Definition of Pharmacokinetics

• Defined as "What the body does to the drug"

• Involves study of the time course of ADME (Absorption, Distribution, Metabolism, Excretion).

• Clinical pharmacokinetics applies pharmacokinetic principles to therapeutic management of drugs in patients.

• The term combines Greek pharmakon (drugs) and kinetics (study of variable changes over time).

Applications of Pharmacokinetics

• Bioavailability measurements

• Physiological/pathological effects on drug disposition

• Dosage adjustments in disease states

• Correlation of pharmacological responses with doses

• Drug interactions evaluation

• Clinical prediction: uses pharmacokinetic parameters for individual drug dosing regimens

Sampling of Biologic Specimens

Invasive Methods

• Require parenteral/surgical interventions

• Examples: Blood, spinal fluid, tissue biopsy

Non-Invasive Methods

• No surgical intervention required

• Examples: Urine, saliva, feces, expired air

• Measurement of drug and metabolite concentrations in serum/plasma is direct; urine is indirect.

LC-MS: Quantifying Pharmaceuticals

• LC-MS (Liquid Chromatography-Mass Spectrometry) is used for drug analysis.

• Involves mobile phase (solvents), multiple component mixtures, and mass spectrometer.

Key Pharmacokinetic Concepts

Onset & Duration of Action

• Onset of Action: Time when drug reaches therapeutic range and effects begin.

• Duration of Action: Span from onset to termination.

• Termination of Action: When plasma concentration falls below minimum effective concentration (MEC).

Therapeutic Range

• Range of plasma concentration likely to produce therapeutic activity with minimum toxicity.

• Terms:

  • MTC: Minimum toxic concentration

  • MEC: Minimum effective concentration

Administration Methods

Oral vs. Intravenous

• Differences in absorption profiles and kinetics after administration

Key Pharmacokinetics Parameters

Tmax

• Time at maximum drug concentration in plasma

Cmax

• Maximum drug concentration related to dosage and absorption rates

AUC (Area Under Curve)

• Reflects amount absorbed systemically (bioavailability)

Pharmacokinetic Models

• Use compartmental models to describe drug behavior: one-compartment, two-compartment, multi-compartment.

• These models categorize drug dynamics but do not represent specific tissues.

One-Compartment Model

• Common in clinical practice—entire body treated as one compartment.

Example: Aminoglycosides

• Good description for drugs with limited distribution.

• Aminoglycosides remain primarily in extracellular water due to their polar nature.

Two-Compartment Model

• Differentiates between central (plasma) and peripheral (tissue) compartments.

Example: Digoxin

• Well described by two-compartment pharmacokinetics; shows rapid plasma decline post IV administration as it distributes to tissues.

Volume of Distribution (V)

• Relates amount of drug in the body to concentration measured in plasma.

• Standard for 70-kg male:

  • 15-18 L = limited to extracellular fluid

  • 40 L = distributed in body water

  • 40-50 L = concentrated in tissues

• Equation: V = X / C

Clearance

• Measure of drug removal from body, expressed as volume/time (L/h or mL/min).

• Total body clearance = sum of individual organ clearances.

Determining Clearance

• Efficient organs approach 100% extraction ratios.

Example: Propranolol

• High extraction ratio indicates significant first-pass metabolism.

Elimination Types

First-Order

• Rate of elimination proportional to drug amount in the body.

Zero-Order

• Rate of elimination constant regardless of drug concentration.

Summary

• Pharmacokinetics concerns the timing of drug ADME.

• Frequent use of the one-compartment model in practice.

• Importance of volume of distribution and clearance in determining pharmacokinetics.

Glossary of Pharmacokinetic Terms

• AUC: Area under concentration vs. time curve.

• Bioavailability (F): Drug dosage reaching systemic circulation.

• Clearance (CL): Rate of drug removal from plasma.

• Cmax: Peak plasma concentration.

• First-order elimination: Amount eliminated depends on remaining drug concentration.

• Half-life (T1/2): Time for plasma concentration to decrease by half.

• Steady State: Dosage equals elimination post multiple doses.

• V: Volume of distribution, measures distribution extent.