Effect of antacid on absorption of the quinolone lomefloxacin.
The effect of antacid on the absorption of lomefloxacin (LFLX) in humans was studied. When LFLX was orally administered concomitantly with aluminum- and magnesium-containing antacids under fasting conditions, its level in plasma decreased by one-half and its area under the concentration-time curve was reduced by 40% compared with the levels observed after treatment with LFLX alone. The urinary recovery value also decreased by 40%. No such effects were noted after coadministration of LFLX and a nonmetallic antacid. This study confirmed the existence of chelate complexes of LFLX with Al3+ and Mg2+ and examined the chelating strength. The stability constants of LFLX with Al3+ and Mg2+ were measured and compared with those of ofloxacin and norfloxacin; little difference was observed among them. LFLX was found to bind more strongly with Al3+ than with Mg2+. Further, the existence of chelate formation was proven by 13C-nuclear magnetic resonance spectroscopy. The decrease in the LFLX level in plasma in humans could be explained by a reduced absorption of the Al(3+)- and Mg(2+)-LFLX chelate complexes.
Shimada
J
J
St. Marianna University School of Medicine, Institute of Medical Science, Kanagawa, Japan.
Shiba
K
K
Oguma
T
T
Miwa
H
H
Yoshimura
Y
Y
Nishikawa
T
T
Okabayashi
Y
Y
Kitagawa
T
T
Yamamoto
S
S
D000328:Adult; D000535:Aluminum / Q000493:pharmacokinetics; D000863:Antacids / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D002614:Chelating Agents / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D024841:Fluoroquinolones; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D008274:Magnesium / Q000493:pharmacokinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D015363:Quinolones / Q000737:chemistry / Q000493:pharmacokinetics*
D000863:Antacids; D000890:Anti-Infective Agents; D002614:Chelating Agents; D024841:Fluoroquinolones; D015363:Quinolones; D000535:Aluminum; D008274:Magnesium; C053091:lomefloxacin