title: Animal versus human oral drug bioavailability: do they correlate?
abstract: Oral bioavailability is a key consideration in development of drug products, and the use of preclinical species in predicting bioavailability in human has long been debated. In order to clarify whether any correlation between human and animal bioavailability exist, an extensive analysis of the published literature data was conducted. Due to the complex nature of bioavailability calculations inclusion criteria were applied to ensure integrity of the data. A database of 184 compounds was assembled. Linear regression for the reported compounds indicated no strong or predictive correlations to human data for all species, individually and combined. The lack of correlation in this extended dataset highlights that animal bioavailability is not quantitatively predictive of bioavailability in human. Although qualitative (high/low bioavailability) indications might be possible, models taking into account species-specific factors that may affect bioavailability are recommended for developing quantitative prediction.
authors.affiliation: Simcyp Limited (a Certara Company), Blades Enterprise Centre, John Street, Sheffield S2 4SU, UK. Electronic address: h.musther@simcyp.com.
authors.forename: Helen
authors.initials: H
authors.lastname: Musther
authors.affiliation: Centre for Applied Pharmacokinetic Research, School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, UK. Electronic address: andres.olivaresmorales@manchester.ac.uk.
authors.forename: Andrés
authors.initials: A
authors.lastname: Olivares-Morales
authors.affiliation: Centre for Applied Pharmacokinetic Research, School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, UK. Electronic address: oliver.hatley@postgrad.manchester.ac.uk.
authors.forename: Oliver J D
authors.initials: OJ
authors.lastname: Hatley
authors.affiliation: Simcyp Limited (a Certara Company), Blades Enterprise Centre, John Street, Sheffield S2 4SU, UK. Electronic address: b.liu@simcyp.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Simcyp Limited (a Certara Company), Blades Enterprise Centre, John Street, Sheffield S2 4SU, UK; Centre for Applied Pharmacokinetic Research, School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, UK. Electronic address: amin.rostami@manchester.ac.uk.
authors.forename: Amin
authors.initials: A
authors.lastname: Rostami Hodjegan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001702:Biopharmaceutics / Q000379:methods*; D006801:Humans; D016014:Linear Models; D023421:Models, Animal; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D010599:Pharmacokinetics; D013045:Species Specificity
chemical_list: D004364:Pharmaceutical Preparations
keywords: Drug development; First in man pharmacokinetics; Oral drug absorption