title: Variability in bioavailability of small molecular tyrosine kinase inhibitors.
abstract: Small molecular tyrosine kinase inhibitors (smTKIs) are in the centre of the very quickly expanding area of personalized chemotherapy and oral applicability thereof. The number of drugs in this class is rapidly growing, with twenty current approvals by both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA). The drugs are, however, generally characterized by a poor oral, and thus variable, bioavailability. This results in significant variation in plasma levels and exposure. The cause is a complex interplay of factors, including poor aqueous solubility, issued permeability, membrane transport and enzymatic metabolism. Additionally, food and drug-drug interactions can play a significant role. The issues related with an impaired bioavailability generally receive little attention. To the best of our knowledge, this article is the first to provide an overview of the factors that determine the bioavailability of the smTKIs.
authors.affiliation: Department of Pharmacy and Pharmacology, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Louwesweg 6, 1006 BK Amsterdam, The Netherlands. Electronic address: Maikel.Herbrink@slz.nl.
authors.forename: Maikel
authors.initials: M
authors.lastname: Herbrink
authors.affiliation: Department of Pharmacy and Pharmacology, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Louwesweg 6, 1006 BK Amsterdam, The Netherlands.
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Nuijen
authors.affiliation: Department of Pharmacy and Pharmacology, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Louwesweg 6, 1006 BK Amsterdam, The Netherlands; Department of Pharmaceutical Sciences, Science Faculty, Utrecht University, Utrecht, The Netherlands.
authors.forename: Jan H M
authors.initials: JH
authors.lastname: Schellens
authors.affiliation: Department of Pharmacy and Pharmacology, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Louwesweg 6, 1006 BK Amsterdam, The Netherlands; Department of Pharmaceutical Sciences, Science Faculty, Utrecht University, Utrecht, The Netherlands.
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors
keywords: Bioavailability; Chemotherapy; Pharmacokinetics; Tyrosine kinase inhibitors