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.

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