Introduction of Biopharmaceutics & Pharmacokinetics

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)

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

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

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

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

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

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

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

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

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

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 Need to refine this slide with some more graphics 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 DCT: only 10 % reabsorbed, impermeable to water, leads to further dilution of filtrate

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

THANK YOU -PHARMA STREET