title: Effects of an Al(3+)- and Mg(2+)-containing antacid, ferrous sulfate, and calcium carbonate on the absorption of nemonoxacin (TG-873870) in healthy Chinese volunteers.
abstract: OBJECTIVE
  To evaluate the effects of an Al(3+)- and Mg(2+)-containing antacid, ferrous sulfate, and calcium carbonate on the absorption of nemonoxacin in healthy humans.
  
  
  METHODS
  Two single-dose, open-label, randomized, crossover studies were conducted in 24 healthy male Chinese volunteers (12 per study). In Study 1, the subjects orally received nemonoxacin (500 mg) alone, or an antacid (containing 318 mg of Al(3+) and 496 mg of Mg(2+)) plus nemonoxacin administered 2 h before, concomitantly or 4 h after the antacid. In Study 2, the subjects orally received nemonoxacin (500 mg) alone, or nemonoxacin concomitantly with ferrous sulfate (containing 60 mg of Fe(2+)) or calcium carbonate (containing 600 mg of Ca(2+)).
  
  
  RESULTS
  Concomitant administration of nemonoxacin with the antacid significantly decreased the area under the concentration-time curve from time 0 to infinity (AUC0-∞) for nemonoxacin by 80.5%, the maximum concentration (Cmax) by 77.8%, and urine recovery (Ae) by 76.3%. Administration of nemonoxacin 4 h after the antacid decreased the AUC0-∞ for nemonoxacin by 58.0%, Cmax by 52.7%, and Ae by 57.7%. Administration of nemonoxacin 2 h before the antacid did not affect the absorption of nemonoxacin. Administration of nemonoxacin concomitantly with ferrous sulfate markedly decreased AUC0-∞ by 63.7%, Cmax by 57.0%, and Ae by 59.7%, while concomitant administration of nemonoxacin with calcium carbonate mildly decreased AUC0-∞ by 17.8%, Cmax by 14.3%, and Ae by 18.4%.
  
  
  CONCLUSIONS
  Metal ions, Al(3+), Mg(2+), and Fe(2+) markedly decreased the absorption of nemonoxacin in healthy Chinese males, whereas Ca(2+) had much weaker effects. To avoid the effects of Al(3+) and Mg(2+)-containing drugs, nemonoxacin should be administered ≥2 h before them.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Yi-fan
authors.initials: YF
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xiao-jian
authors.initials: XJ
authors.lastname: Dai
authors.affiliation: The First Hospital Affiliated to Lanzhou University, Lanzhou 730000, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Chen
authors.affiliation: The First Hospital Affiliated to Lanzhou University, Lanzhou 730000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.affiliation: The First Hospital Affiliated to Lanzhou University, Lanzhou 730000, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Qiao
authors.affiliation: TaiGen Biotechnology Co Ltd, Taipei 11470, Taiwan, China.
authors.forename: Cheng-yuan
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: TaiGen Biotechnology Co Ltd, Taipei 11470, Taiwan, China.
authors.forename: Li-wen
authors.initials: LW
authors.lastname: Chang
authors.affiliation: TaiGen Biotechnology Co Ltd, Taipei 11470, Taiwan, China.
authors.forename: Ping-ting
authors.initials: PT
authors.lastname: Huang
authors.affiliation: TaiGen Biotechnology Co Ltd, Taipei 11470, Taiwan, China.
authors.forename: Chiung-yuan
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: TaiGen Biotechnology Co Ltd, Taipei 11470, Taiwan, China.
authors.forename: Yu-ting
authors.initials: YT
authors.lastname: Chang
authors.affiliation: TaiGen Biotechnology Co Ltd, Taipei 11470, Taiwan, China.
authors.forename: Chen-en
authors.initials: CE
authors.lastname: Tsai
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Da-fang
authors.initials: DF
authors.lastname: Zhong
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000536:Aluminum Hydroxide / Q000008:administration & dosage*; D000863:Antacids / Q000008:administration & dosage*; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D002119:Calcium Carbonate / Q000008:administration & dosage*; D002681:China; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005296:Ferrous Compounds / Q000008:administration & dosage*; D065569:Gastrointestinal Absorption / Q000187:drug effects*; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D008276:Magnesium Hydroxide / Q000008:administration & dosage*; D008297:Male; D008657:Metabolic Clearance Rate; D015363:Quinolones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000863:Antacids; D000890:Anti-Infective Agents; D005296:Ferrous Compounds; D015363:Quinolones; C020748:ferrous sulfate; D000536:Aluminum Hydroxide; D002119:Calcium Carbonate; D008276:Magnesium Hydroxide; C543520:nemonoxacin