5501: Intro to Pharmacokinetics

Drug-Body Interactions

Oral Administration of Drug> plasma/protein complex, adipose tissue, effector tissue, peripheral tissues via metabolism, Liver( –>bile), Kidney…

Liver is a big defense of the body, it metabolizes most of the drugs (Cyps).

Complex picture of drug interactions in the body. Many of these processes maybe fast or not significant for any given drug.

Drug-Body Relationship
Pharmacokinetics (PK)
Pharmacodynamics (PD)

*what the drug does to the body.*

It refers to the relationship between drug concentration at the site of action and pharmacological response, i.e., the intensity and time course of therapeutic and adverse effects.

Pharmacodynamics (PD)

The study of physiological effects of drugs and their mechanism of action

*what the body does to the drug.*
How drugs move around the body?
How quickly this movement occurs?
Pharmacokinetics

The study of the time course of drug *Absorption (except for the IV route), Distribution, Metabolism and Excretion (ADME).*

refers to the fate of a drug after its absorption
Drug Disposition
-Distribution
-Metabolism
-Excretion

The combined process of drug metabolism and excretion is also called
*drug elimination*

Although the drug concentration at the site of action determines response, ________________ can often be related to response since drug diffuse from plasma to the site of action.
*plasma drug concentration*

What factors can cause changes in pharmacokinetics of drugs that may affect the outcome of drug therapy.
Diseases, age, genetic, and ethnic differences

The study of pharmacokinetic differences of drugs in various population groups is referred as
Population Pharmacokinetics

PK studies are involved in all phases of drug R&D.
Understand *slide 11*
Animal Testing? Phase I > Phase II > Phase III

From Fadi’s lecture on FDA trial process…
Discovery phase or Animal testing –>the to P1(stability) –>P2 (efficacy)–> P3 (efficacy)
*stability is the most important*

The study of pharmacokinetics involves both
*experimental and theoretical aspects*

involves the development of biological sampling techniques, analytical methods for the determination of drugs and their metabolites, and the procedures that facilitate data collection.
*experimental aspect*

Classical pharmacokinetics is a study of theoretical models focusing mostly on
*model development and parameterization*

Drug concentrations in biological samples are determined by analytical methods.

Analytical methods need to be ________

*specific, sensitive and precise.*

Sensitive assay can measure drug at low concentrations.
Specific assay can distinguish drug from other interference.
Precise assay can provide accuracy and reproducibility.

Commonly Used Analytical Methods
High-performance liquid chromatography (HPLC)
HPLC/MS (mass spectrometry) and LC/MS/MS
Gas chromatography (GC)
GC/MS
Spectrophotometry
Radioimmunoassay
Enzyme multiplied immunoassay

PK Modeling

Many of the processes involved in drug movement around the body are

*often not saturated* at normal therapeutic dose levels (*linear kinetics*).

can be used to describe *plasma concentration as a function of time.*
*Pharmacokinetic – mathematical models*

PK Applications are used to
To design dosage regimen (how much, how often) in patient, that can achieve the maximum therapeutic effect with minimal side effects.

To assess the relationship between drug concentration and pharmacological activities. This helps to understand magnitude of therapeutic and toxic responses at different dosage levels.

To establish bioequivalence i.e., to check whether different formulations will produce the same plasma drug concentrations or not, and therefore will produce similar therapeutic effects.

The application of pharmacokinetic principles to the safe and effective therapeutic management of patients is
Clinical Pharmacokinetics

It involves a multidisciplinary approach to *individually optimized dosing strategies* based on the patient’s disease state and patient-specific considerations.

The magnitude of both the *desired response and toxicity* are functions of the drug concentration at the site of action (and plasma drug concentration).
Principle of Clinical PK

The therapeutic failure results when either the concentration is too low, giving ineffective therapy, or is too high which will produce toxicity.

Between these limits of concentration lies a region associated with therapeutic success; this region is regarded as _______.

*therapeutic window*

*therapeutic concentration range*
A range of drug concentration which produces therapeutic success

Therapeutic range: 10-20 mg/L for Phenytoin, why is there a range?
Drug management differs for everyone
*Individual Variations*

Determination of plasma concentrations to optimize a patient’s drug therapy is know as
therapeutic drug monitoring (TDM)

TDM is essential for drugs with narrow therapeutic widow such as *phenytoin, digoxin, lidocaine, theophilline.*

*Memorize* and practice practice practice