Role of drug transporters in rational use of drugs at high altitude area

Abstract

Pharmacokinetics plays a key role in rational use of medicines. Many factors can affect the drug's pharmacokinetics. Previous studies mainly focused on the impact of hypoxia on hepatic drug metabolizing enzyme, but uncommon on drug transporters. Actually, drug transporter is a key factor for activation of the drugs transport across the cell membrane into the inside of cells, such as multidrug resistance protein (MDR), breast cancer resistance protein (BCRP), multidrug resistance associated protein (MRP), organic cation transporter (OCT), organic anion-transporting polypeptide (OATP), organic anion transporter (OAT), qligopeptide transporter (PEPT), etc. They are widely present in the small intestine villus epithelial cells, renal tubular epithelial cells, hepatocytes and biliary epithelial cells. They play a very important role in drug absorption, distribution, metabolism and excretion. The changes in drug transporters under hypoxia in intestinal could affect the bioavailability of drugs; the changes in drug transporters in organs could affect drug's distribution, subsequent drug's indications and adverse reactions; the changes in drug transporters in liver and kidney could affect the metabolism and excretion rate of drugs, thereby the drug's residence time and half-life.