1. Introduction of Biopharmaceutics & Pharmacokinetics

2. So what is this course about ??
Bio-pharmaceutics
Pharmacokinetics
DCT: only 10 % reabsorbed, impermeable to water, leads to further dilution of filtrate
Here we will study factors affecting the entry of drugs
Here we will study kinetic’s of drug movement (both entry & exit out of body)

3. So how is the course organized??
Factors affecting Drug Entry
Drug Distribution
Drug Elimination
Mathematical Concepts in PK
Concepts in Bioavailability/BE
DCT: only 10 % reabsorbed, impermeable to water, leads to further dilution of filtrate

4. Biopharmaceutics Drug response depends on several variables
Route of administration
Different dosage forms
Physico-chem properties
Excipients
DCT: only 10 % reabsorbed, impermeable to water, leads to further dilution of filtrate

5. 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
Excipients
DCT: only 10 % reabsorbed, impermeable to water, leads to further dilution of filtrate
Optimize drug efficacy

6. Important role of Biopharmaceutics in Drug discovery & development
Solubility
Formulations
Pro--Drugs
Manufacturing process
Crystalline state
Development
Discovery
Particle Size
DCT: only 10 % reabsorbed, impermeable to water, leads to further dilution of filtrate
Dissolution Rate
Stability
Stereo-Chem Factors
Salt Formation
Permeability

7. Important role of Biopharmaceutics in Drug discovery & development
Brivanib (BMS ) 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
DCT: only 10 % reabsorbed, impermeable to water, leads to further dilution of filtrate

8. 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, That’s what the company did. They developed a micro-particle formulation that increased overall solubility
DCT: only 10 % reabsorbed, impermeable to water, leads to further dilution of filtrate

9. 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
DCT: only 10 % reabsorbed, impermeable to water, leads to further dilution of filtrate

10. Pharmacokinetics (PK)
For a better, safe use of drugs we need to know
Absorption
Distribution
Metabolism
Excretion
Rate & Mechanism of ADME
DCT: only 10 % reabsorbed, impermeable to water, leads to further dilution of filtrate

11. Pharmacokinetics Definition of Pharmacokinetics:
Study of time course of ADME and their relationship with therapeutic and toxic effects of drug
DCT: only 10 % reabsorbed, impermeable to water, leads to further dilution of filtrate

12. Role of PK in drug discovery
AIKTC-123 has a good anti-cancer activity in animals. we need to know what’s an effective dose in humans ??
We know effective drug from animal studies
Understand overall PK in animals
Predict what is PK in humans
Understand Metabolism/Excretion in animals
We know PK in humans
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We know then calculate dose needed to get effect

13. 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
DCT: only 10 % reabsorbed, impermeable to water, leads to further dilution of filtrate

14. 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
DCT: only 10 % reabsorbed, impermeable to water, leads to further dilution of filtrate

15. THANK YOU -PHARMA STREET