健常人における長時間作用型ニューキノロン剤スパルフロキサシンの尿中排せつに及ぼす金属カチオンの影響

Abstract

Sparfloxacin (SPFX) is a long-acting new quinolone (NQ) due most probably to its enterohepatic circulation. We examined the drug interaction between sparfloxacin and the metal cation by measuring the urinary excretion of unmetabolized SPFX, and compared the findings with the interaction between norfloxacin (NFXL) and metal cations. The metal cations were found to be antacids containing aluminum and magnesium cations.Urine samples for 12 hrs were collected for three days after the single oral administration of a 100-mg tablet of SPFX or norfloxacin (NFLX) in six healthy volunteers. The drugs were administered in the following four protocols: Control a single oral dose of. the NQ in the morning (A); a single oral dose of the NQ and the antacid simultaneously in the morning (B); a single dose of NQ followed by the antacid 3 times a day for 3 days starting 2 hrs after the NQ administration (C); and the oral dose of NQ and the antacid simultaneously in the morning and then the antacid 3 times a day for 3 days starting 2 hrs after the NQ administration. Urinary excretion of SPFX was still present at 72 hrs whereas that of NFXL was terminated within 24 hrs. The urinary excretion of SPFX for 72-hr period was in the order of Control>A=B>C, while that of NFLX was in the order of Control>B>A>C. In other words, the urinary excretion of SPFX or NFXL are markedly affected even when metal cations were administered 2 hrs after the NQ administration. The urinary excretion of SPFX continued to increase until 72 hrs after the administration in all protocols. Therefore, metal cations may interact with SPFX during the enterohepatic circulation, but it may not largely affect the urinary excretion of SPFX.