Course Catalog

Oral Bioavailability Assessment in Preclinical Species and Human

Poor oral bioavailability is one of the leading causes of compound failure in preclinical and clinical development. Compounds with poor oral bioavailability and short half life tend to have large dose and higher inter and intra-individual variability, which would limit their therapeutic usefulness and increase the cost of their developments. Poor oral bioavailability in preclinical species does not necessarily translate into poor human oral bioavailability and vice versa.

Course Details

Key Topics

• General principles of pharmacokinetics and application that feature LC/MS.
• The parameters that determine oral bioavailability in human.
• Approaches to optimize physicochemical and biopharmaceutical parameters that influence drug solubility, permeability, and metabolism, where applicable.
• Anatomical and physiological factors that lead to species differences in oral bioavailability.
• The state-of-the-art in vitro and in vivo ADME assays, and how pharmacokinetics, and drug metabolism and transporter research studies are conducted to select the candidates to advance in preclinical and clinical development.
• The utility of validated physiologically based pharmacokinetics (PBPK) modeling during discovery and development of drug candidates.
• The use of Biopharmaceutics Drug Disposition Classification System (BDDCS) in predicting drug disposition, drug-drug interaction, and impact of food on the pharmacokinetic profile of new chemical entities (NCEs).
• The workshop will also include a hands-on sessions that aim at improving your ability to apply these strategies to medicinal chemistry for hit selection, lead optimization, and development candidate selection.

Information

Poor oral bioavailability is one of the leading causes of compound failure in preclinical and clinical development. Compounds with poor oral bioavailability and short half life tend to have large dose and higher inter and intra-individual variability, which would limit their therapeutic usefulness and increase the cost of their developments. Poor oral bioavailability in preclinical species does not necessarily translate into poor human oral bioavailability and vice versa.

Who Should Attend

This practical/hands on course is specifically designed for personnel in the pharmaceutical and biotechnology industries and contract research organizations (CROs)

Agenda

  • Pharmacokinetics and LC/MS Applications
    • Pharmacokinetics definition
    • Zero and first order kinetics
    • Non-compartmental and compartmental modeling
    • Physiologically based pharmacokinetics modeling
    • Area under the curve (AUC)
    • Cmax and Tmax
    • Absorption rate constant (Ka)
    • Volume of distribution (Vd)
    • Clearance (CL)
    • Half life (T1/2)
  • Drug ADME
    • Factors affecting oral absorption
      • Gastrointestinal Tract “GIT” surface area
      • GIT pH
    • Factors affecting drug distribution
      • Perfusion vs. permeability rate limited
      • Physicochemical factors influencing drug distribution
      • Physiologic factors influencing drug distribution
    • Metabolism
      • Phase I and II reactions
    • Routes of excretion
      • Renal excretion
      • Biliary excretion
      • Enterohepatic circulation
  • Oral bioavailability
    • Oral bioavailability definition
    • Oral bioavailability calculation
    • Absorption impact on oral bioavailability
      • The mechanism of drug oral absorption
      • Approaches to increase drug solubility
      • pKa
      • Ionization
      • Lipophilicity
      • Hydrogen bonding
      • Out of plane substitution
    • Approaches to increase drug dissolution
      • Particle size and its impact on drug dissolution
      • The use of nanoparticle in overcoming poor dissolution
      • The use of spray dried dispersion in overcoming poor dissolution
      • Amorphous drug
      • pH and salt interplay
      • Polymorphism
      • Drug complexation
    • Hands on Q&A: Session I
  • Impact of efflux and influx transporters on oral bioavailability and Fa
    • Impact of efflux transporters on oral bioavailability and Fa
      • Impact of p-glycoprotein (pgp) on oral bioavailability and Fa
      • Impact of Breast Cancer Resistance Protein (BCRP) on oral bioavailability and Fa
      • Impact of Multidrug Resistant Associated Protein 2 (MRP2) on oral bioavailability and Fa
      • Sensitivity analysis of factors that influence efflux transporter (pgp) impact on oral drug Absorption
    • Impact of influx transporters on oral bioavailability and Fa
      • Impact of Organic Anion Transporting Polypeptide 2B1 (OATP2B1) on oral bioavailability and Fa
      • Impact of Peptide Transporter 1 (PEPT1) on oral bioavailability and Fa
      • Impact of Monocarboxylate Transporter 1 (MCT1) on oral bioavailability and Fa
      • The relationship between transporter capacity and affinity to drug dose
      • Species differences in the GIT anatomy and physiology with their impact on oral bioavailability
  • Impact of first pass on oral bioavailability
    • First pass definition
    • Impact of species differences on drug hepatic elimination and oral bioavailability
    • Intestinal metabolism and its impact on first pass and oral bioavailability
    • Variables affecting intestinal metabolism and approaches to calculate Fg using CLint,h
  • Biopharmaceutics Drug Disposition Classification System (BDDCS)
    • Definition of BDDCS and its utility in drug discovery and development
    • Use of BDDCS in determining the route of elimination for new chemical entities (NCEs)
    • Projection of drug-drug interaction liability using BDDCS
  • Approaches to assess poor oral bioavailability issues
    • PBPK modeling
    • Caco-2 and MDCK cell lines
    • In situ rat intestinal perfusion
    • In vivo approaches
      • AUC comparison between oral and intravenous administration
      • Mass balance
      • Clearance method
      • Dose proportionality studies
      • The use of 1-aminobenzotriazole in assessing the contribution of first pass to the oral bioavailability of drugs
    • Approaches to assess the pharmacodynamic activity of NME with poor oral bioavailability
      • Intraperitoneal (IP) dosing
      • Subcutaneous (SC) dosing
      • Challenges with IP and SC dosing
    • Hands on Q&A: Session II

Course Locations

Date

TBA

Check-in opens at 7:30 a.m. on the day of the course.
Course runs from 8:30 a.m. to 5:00 p.m.

Register Via Mail

Venue

The course fee includes a course binder and a continental breakfast.

Five for Four! Register five people for one course, one person for five courses, or any combination in between and your fifth registration is free. Note: This discount is only available if you register by fax or mail and mention this discount. May not be combined with any other offer.


Pricing
  Member Non-Member
Advanced $895 $1,095
Standard $1,095 $1,295

About the Instructors

  • Mike Lee

    is a biotechnology entrepreneur and Founder and President of Milestone Development Services. He actively participates in the development of new technologies and their integration into industrial settings. Dr. Lee has more than 25 years of pharmaceutical industry experience. He has pioneered the application of LC/MS for research dealing with biomolecules, optimization of ADME and physicochemical properties, natural products, drug metabolites, impurities, and degradants.

  • Ayman El-Kattan

    is Associate Research Fellow at the Pharmacokinetics, Dynamics, and Metabolism Department, Pfizer Inc. Groton Laboratories.