School of Pharmacy
Basic Pharmacokinetics
Instructor: Sharan Bobbala, Ph.D.
Definition of pharmacokinetics and applications
Pharmacokinetic models
Volume of distribution
Clearance
First-order and zero-order elimination
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.
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).
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
Require parenteral/surgical interventions
Examples: Blood, spinal fluid, tissue biopsy
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 (Liquid Chromatography-Mass Spectrometry) is used for drug analysis.
Involves mobile phase (solvents), multiple component mixtures, and mass spectrometer.
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).
Range of plasma concentration likely to produce therapeutic activity with minimum toxicity.
Terms:
MTC: Minimum toxic concentration
MEC: Minimum effective concentration
Differences in absorption profiles and kinetics after administration
Time at maximum drug concentration in plasma
Maximum drug concentration related to dosage and absorption rates
Reflects amount absorbed systemically (bioavailability)
Use compartmental models to describe drug behavior: one-compartment, two-compartment, multi-compartment.
These models categorize drug dynamics but do not represent specific tissues.
Common in clinical practice—entire body treated as one compartment.
Good description for drugs with limited distribution.
Aminoglycosides remain primarily in extracellular water due to their polar nature.
Differentiates between central (plasma) and peripheral (tissue) compartments.
Well described by two-compartment pharmacokinetics; shows rapid plasma decline post IV administration as it distributes to tissues.
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
Measure of drug removal from body, expressed as volume/time (L/h or mL/min).
Total body clearance = sum of individual organ clearances.
Efficient organs approach 100% extraction ratios.
High extraction ratio indicates significant first-pass metabolism.
Rate of elimination proportional to drug amount in the body.
Rate of elimination constant regardless of drug concentration.
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.
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.