title: Modulation of pharmacokinetics of theophylline by antofloxacin, a novel 8-amino-fluoroquinolone, in humans.
abstract: OBJECTIVE
  To evaluate the pharmacokinetic interactions between theophylline and antofloxacin in vivo and in vitro.
  
  
  METHODS
  A randomized, 5-day treatment and 3-way crossover design was documented in 12 healthy subjects. The subjects were orally administered with antofloxacin (400 mg on d 1 and 200 mg on d 2 to 5), theophylline (100 mg twice a day and morning dose 200 mg on d 1 and 5), or theophylline plus antofloxacin. The plasma and urinary pharmacokinetics of antofloxacin and theophylline were characterized after the first and last dose. The effect of antofloxacin on theophylline metabolism was also investigated in pooled human liver microsomes.
  
  
  RESULTS
  The 5-day treatment with antofloxacin significantly increased the area of the plasma concentration-time curve and peak plasma concentration of theophylline, accompanied by a decrease in the excretion of theophylline metabolites. On the contrary, theophylline did not affect the pharmacokinetics of antofloxacin. In vitro studies using pooled human hepatic microsomes demonstrated that antofloxacin was a weak reversible and mechanism-based inhibitor of CYP1A2. The clinical interaction between theophylline and antofloxacin was further validated by the in vitro results.
  
  
  CONCLUSIONS
  The results showed that antofloxacin increases the plasma theophylline concentration, partly by acting as a mechanism-based inhibitor of CYP1A2.
authors: Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
authors: Li
authors: L
authors: Liu
authors: Xian
authors: X
authors: Pan
authors: Hai-yan
authors: HY
authors: Liu
authors: Xiao-dong
authors: XD
authors: Liu
authors: Hui-wen
authors: HW
authors: Yang
authors: Lin
authors: L
authors: Xie
authors: Jun-lin
authors: JL
authors: Cheng
authors: Hong-wei
authors: HW
authors: Fan
authors: Da-wei
authors: DW
authors: Xiao
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D001993:Bronchodilator Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D018592:Cross-Over Studies; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D015242:Ofloxacin / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000652:urine; D013806:Theophylline / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D001993:Bronchodilator Agents; D065609:Cytochrome P-450 CYP1A2 Inhibitors; C522674:antofloxacin; D015242:Ofloxacin; D013806:Theophylline; D019388:Cytochrome P-450 CYP1A2