Effects of an Al super(3+)- and Mg super(2+)-containing antacid, ferrous sulfate, and calcium carbonate on the absorption of nemonoxacin (TG-873870) in healthy Chinese volunteers

Aim: To evaluate the effects of an Al super(3+)- and Mg super(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 super(3+) and 496 mg of Mg super(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 super(2+)) or calcium carbonate (containing 600 mg of Ca super(2+)). Results: Concomitant administration of nemonoxacin with the antacid significantly decreased the area under the concentration-time curve from time 0 to infinity (AUC sub(0- infinity )) for nemonoxacin by 80.5%, the maximum concentration (C sub(max)) by 77.8%, and urine recovery (Ae) by 76.3%. Administration of nemonoxacin 4 h after the antacid decreased the AUC sub(0- infinity ) for nemonoxacin by 58.0%, C sub(max) 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 AUC sub(0- infinity ) by 63.7%, C sub(max) by 57.0%, and Ae by 59.7%, while concomitant administration of nemonoxacin with calcium carbonate mildly decreased AUC sub(0- infinity ) by 17.8%, C sub(max) by 14.3%, and Ae by 18.4%. Conclusion: Metal ions, Al super(3+), Mg super(2+), and Fe super(2+) markedly decreased the absorption of nemonoxacin in healthy Chinese males, whereas Ca super(2+) had much weaker effects. To avoid the effects of Al super(3+) and Mg super(2+)-containing drugs, nemonoxacin should be administered greater than or equal to 2 h before them.