The road map to oral bioavailability: an industrial perspective.
Optimisation of oral bioavailability is a continuing challenge for the pharmaceutical and biotechnology industries. The number of potential drug candidates requiring in vivo evaluation has significantly increased with the advent of combinatorial chemistry. In addition, drug discovery programmes are increasingly forced into more lipophilic and lower solubility chemical space. To aid in the use of in vitro and in silico tools as well as reduce the number of in vivo studies required, a team-based discussion tool is proposed that provides a 'road map' to guide the selection of profiling assays that should be considered when optimising oral bioavailability. This road map divides the factors that contribute to poor oral bioavailability into two interrelated categories: absorption and metabolism. This road map provides an interface for cross discipline discussions and a systematic approach to the experimentation that drives the drug discovery process towards a common goal - acceptable oral bioavailability using minimal resources in an acceptable time frame.
Thomas
V Hayden
VH
Pfizer Global Research and Development, Department of Pharmaceutical Sciences, Ann Arbor, MI 48105, USA.
Bhattachar
Shobha
S
Hitchingham
Linda
L
Zocharski
Philip
P
Naath
Maryanne
M
Surendran
Narayanan
N
Stoner
Chad L
CL
El-Kattan
Ayman
A
D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004345:Drug Industry; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D012995:Solubility
D004364:Pharmaceutical Preparations