Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs.
Article Details
- CitationCopy to clipboard
Faassen F, Vogel G, Spanings H, Vromans H
Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs.
Int J Pharm. 2003 Sep 16;263(1-2):113-22.
- PubMed ID
- 12954186 [ View in PubMed]
- Abstract
In this study the gastrointestinal absorption and P-glycoprotein (Pgp) efflux transport of heterocyclic drugs was investigated with the Caco-2 cell model. Based on the calculation of the physico-chemical properties a good oral absorption was predicted for all the drugs tested in this study which corresponded well with the measured Caco-2 permeabilities (Papp). Generally a high permeability of the tested heterocyclic drugs was measured being in agreement with earlier published human in vivo absorption data. Based on the transport data of domperidone and verapamil it was found that the Pgp efflux transporter was expressed in the Caco-2 cells. Many of the drugs tested were indicated to be potential Pgp efflux substrates. Since Pgp is expressed at the Blood Brain Barrier (BBB) as well, it was expected that CNS penetration will be impaired if a drug is a Pgp substrate. However, no correlation could be found between brain penetration in rats and the Pgp efflux ratio as measured with the Caco-2 cells. From the data it is concluded that Pgp efflux ratio's as determined in in vitro High Throughput Screening (HTS) tests, where the transport conditions are fixed (pH gradient, concentration, etc.), cannot routinely be used to predict a possible limited brain penetration.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Acetaminophen P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorDetails Acetylsalicylic acid P-glycoprotein 1 Protein Humans UnknownSubstrateInducerModulatorDetails Carbamazepine P-glycoprotein 1 Protein Humans UnknownInducerDetails Dexibuprofen P-glycoprotein 1 Protein Humans UnknownNot Available Details Domperidone P-glycoprotein 1 Protein Humans UnknownSubstrateDetails Ibuprofen P-glycoprotein 1 Protein Humans UnknownSubstrateDetails Imipramine P-glycoprotein 1 Protein Humans UnknownSubstrateDetails Indomethacin P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorDetails Quinidine P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorDetails Ranitidine P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorDetails