Drug transporters in the lung--do they play a role in the biopharmaceutics of inhaled drugs?
The role of transporters in drug absorption, distribution and elimination processes as well as in drug-drug interactions is increasingly being recognised. Although the lungs express high levels of both efflux and uptake drug transporters, little is known of the implications for the biopharmaceutics of inhaled drugs. The current knowledge of the expression, localisation and functionality of drug transporters in the pulmonary tissue and the few studies that have looked at their impact on pulmonary drug absorption is extensively reviewed. The emphasis is on transporters most likely to affect the disposition of inhaled drugs: (1) the ATP-binding cassette (ABC) superfamily which includes the efflux pumps P-glycoprotein (P-gp), multidrug resistance associated proteins (MRPs), breast cancer resistance protein (BCRP) and (2) the solute-linked carrier (SLC and SLCO) superfamily to which belong the organic cation transporter (OCT) family, the peptide transporter (PEPT) family, the organic anion transporter (OAT) family and the organic anion transporting polypeptide (OATP) family. Whenever available, expression and localisation in the intact human tissue are compared with those in animal lungs and respiratory epithelial cell models in vitro. The influence of lung diseases or exogenous agents on transporter expression is also mentioned.
Bosquillon
Cynthia
C
Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, University Park, Nottingham NG72RD, United Kingdom. cynthia.bosquillon@nottingham.ac.uk
D000280:Administration, Inhalation; D000818:Animals; D001702:Biopharmaceutics / Q000379:methods*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018929:Cell Culture Techniques; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008171:Lung Diseases / Q000188:drug therapy* / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism; D014018:Tissue Distribution
D002352:Carrier Proteins; D008565:Membrane Proteins; D004364:Pharmaceutical Preparations