Introduction of

Biopharmaceutics &
Pharmacokinetics
So what is this course about ??

Bio-
Pharmacokinetics
pharmaceutics

Here we will study factors Here we will study kinetics of

affecting the entry of drugs drug movement (both entry &
exit out of body)
So how is the course organized??

Factors Concepts in
Drug Drug Mathematical
affecting Bioavailability/
Distribution Elimination Concepts in PK
Drug Entry BE
 Biopharmaceutics

Drug response depends on several variables

Route of administration
Different dosage forms
Physico-chem properties
Excipients
 Biopharmaceutics

Definition:
Biopharmaceutics is a study of factors affecting rate/amount of drug
reaching systemic circulation

Route of administration
Different dosage forms
Physico-chem properties Optimize drug efficacy
Excipients
 Important role of Biopharmaceutics in Drug
discovery & development

Solubility
Formulations

Pro--Drugs Manufacturing
Crystalline state process

Discovery Development
Particle Size
Dissolution Rate Stability
Stereo-Chem
Factors
Salt Formation Permeability
 Important role of Biopharmaceutics in Drug
discovery & development

Brivanib (BMS-540215) had shown excellent anti-cancer activity in animals & in-vitro
models, however the solubility was very poor.
Poor solubility is known to affect the overall amount of drug entering body.

Solution:

Design a salt form of drug that has a better solubility. The discovery scientist developed
an alaninate salt that had much better solubility & better bioavailability
 Important role of Biopharmaceutics in Drug
discovery & development

Vemurafenib, a blockbuster anti-cancer drug was hitting dose limiting solubility in clinical
trials ( increase of drug did not lead to increase in drug conc due to poor solubility)

Solution:

Particle size of drug is known to affect solubility, can we reduce particle size to increase
solubility, YES, Thats what the company did. They developed a micro-particle formulation
that increased overall solubility
 Important role of Biopharmaceutics in Drug
discovery & development

AIKTC therapeutics has a pain medicine already on market in tablet form, it wants to
develop a sustained release formulation. What information will it need to develop this
new formulation

Solution:

Understand the rate of drug absorption by tablet form, evaluate how sustain release will
affect absorption & ultimately the drug effect
 Pharmacokinetics (PK)

For a better, safe use of drugs we need to know

Absorption
Distribution
Rate & Mechanism of ADME
Metabolism
Excretion
Pharmacokinetics

Definition of Pharmacokinetics:

Study of time course of ADME and their relationship with therapeutic and
toxic effects of drug
 Role of PK in drug discovery

AIKTC-123 has a good anti-cancer activity in animals. we need to know

whats an effective dose in humans ??
We know effective drug from
animal studies

Understand Understand overall Predict what is PK We know PK in humans

Metabolism/Excretion PK in animals in humans
in animals

We know then calculate dose

needed to get effect
Role of PK in drug development

Sunitinib is a anti-cancer drug that is metabolized by

enzyme CYP3A4.
Doctor wants to know if he can give it with another drug
ketoconazole which is CYP3A4 inhibitor

Ketoconazole will inhibit CYP3A4

sunitinib will not be metabolized
increase in concentration of sunitinib, might lead to
toxicity
Role of PK in drug development

Brivanib is a anti-cancer drug that is developed to treat liver cancer

During the clinical trials, the doctor wants to know if he can give it to
patients with liver impairment

Evaluate PK of brivanib in liver impaired patients

See how different the exposure is compared to normal liver patients
Accordingly advise doctors if the dose needs to be changed
THANK YOU
-PHARMA STREET