Carrier-Mediated Tissue Distribution and Blood-Brain Barrier Transport of New Quinolones

Animal and clinical investigations have shown that fluoroquinolones, new quinolone antibacterial agents (NQs), are well absorbed across the intestinal tract, with a bioavailability of 60-90% after oral administration. Although some types of carrier-mediated intestinal transport mechanisms have been reported for enoxacin (ENX), ofloxacin (OFLX) and sparfloxacin (SPFX), recent results using a human intestinal epithelial cell line, Caco-2, indicated a passive or nonsaturable transport of SPFX, one of the most hydrophobic NQs. The mechanism underlying the intestinal absorption of NQs is still largely unknown. The distribution of NQs into peripheral tissues including erythrocytes is very rapid and their tissue-to-plasma concentration ratios (Kp) are considerably larger than those of inulin (an extracellular fluid space marker), in spite of almost complete ionization of NQs at the physiological pH. Our findings suggest that OFLX and lomefloxacin (LFLX) are taken up by rat erythrocytes via a transport system common to that of a water-soluble vitamin, nicotinic acid.