Interaction of swine organic anion transporting polypeptide 1a2 with tetracycline, macrolide and β-lactam antibiotics.

Organic anion-transporting polypeptides (human OATPs; animals Oatps; gene symbol SLCO/Slco) are integral membrane proteins that mediate the sodium-independent transport of a wide range of endogenous compounds as well as many xenobiotics. Antibiotics, antidiabetic drugs, anti-inflammatory drugs, antifungals, antivirals, antihistamines, antihypertensives, fibrates, statins, cardiac glycosides, immunosuppressants, and anticancer drugs are among the substrates transported by OATPs. Because of the broad substrate specificity, wide tissue distribution and the involvement of drug-drug interaction, human OATPs have been extensively recognized as key determinants for drug absorption, distribution and excretion. In a previous study, we cloned a functional orthologue of human OATP1A2 from the pig liver and designated it as swine Oatp1a2 (sOatp1a2) based on sequence analysis and phylogenic study. In the present study, transport capability of swine Oatp1a2 for tetracyclines, macrolides and β-lactam antibiotics was investigated. It was found that most of the tested antibiotics, including the tetracycline family members such as tetracycline, doxycycline, oxytetracycline and chlortetracycline as well as the β-lactam antibiotics such as penicillin, amoxicillin and cefquinome are directly transported by sOatp1a2; while macrolides such as tylosin, tilmicosin, clarithromycin and erythromycin may only inhibit uptake function of the transporter. As a group of well-known inhibitors of OATP family members, the effect of flavonoids on sOatp1a2 function was evaluated and it was found that all the flavonoids tested are inhibitors of the swine transporter as well.