title: Effect of MMX® mesalamine coadministration on the pharmacokinetics of amoxicillin, ciprofloxacin XR, metronidazole, and sulfamethoxazole: results from four randomized clinical trials.
abstract: BACKGROUND
  MMX(®) mesalamine is a once daily oral 5-aminosalicylic acid formulation, effective in induction and maintenance of ulcerative colitis remission. Patients on long-term mesalamine maintenance may occasionally require concomitant antibiotic treatment for unrelated infections.
  
  
  OBJECTIVE
  To evaluate the potential for pharmacokinetic interactions between MMX mesalamine and amoxicillin, ciprofloxacin extended release (XR), metronidazole, or sulfamethoxazole in four open-label, randomized, placebo-controlled, two-period crossover studies.
  
  
  METHODS
  In all four studies, healthy adults received placebo once daily or MMX mesalamine 4.8 g once daily on days 1-4 in one of two treatment sequences. In studies 1 and 2, subjects also received a single dose of amoxicillin 500 mg (N=62) or ciprofloxacin XR 500 mg (N=30) on day 4. In studies 3 and 4, subjects received metronidazole 750 mg twice daily on days 1-3 and once on day 4 (N=30); or sulfamethoxazole 800 mg/trimethoprim 160 mg twice daily on days 1-3 and once on day 4 (N=44).
  
  
  RESULTS
  MMX mesalamine had no significant effects on systemic exposure to amoxicillin, ciprofloxacin, or metronidazole; the 90% confidence intervals (CIs) around the geometric mean ratios (antibiotic + MMX mesalamine: antibiotic + placebo) for maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) fell within the predefined equivalence range (0.80-1.25). Sulfamethoxazole exposure increased by a statistically significant amount when coadministered with MMX mesalamine; however, increased exposure (by 12% in Cmax at steady state; by 15% in AUC at steady state) was not considered clinically significant, as the 90% CIs for each point estimate fell entirely within the predefined equivalence range. Adverse events in all studies were generally mild.
  
  
  CONCLUSIONS
  MMX mesalamine may be coadministered with amoxicillin, ciprofloxacin, metronidazole, or sulfamethoxazole, without affecting pharmacokinetics or safety of these antibiotics.
  
  
  BACKGROUND
  NCT01442688, NCT01402947, NCT01418365, and NCT01469637.
authors.affiliation: Shire, Basingstoke, UK.
authors.forename: David
authors.initials: D
authors.lastname: Pierce
authors.affiliation: Shire, Wayne, PA, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Corcoran
authors.affiliation: Shire, Wayne, PA, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Martin
authors.affiliation: Shire, Basingstoke, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Barrett
authors.affiliation: Shire, Basingstoke, UK.
authors.forename: Susi
authors.initials: S
authors.lastname: Inglis
authors.affiliation: Shire, Wayne, PA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Preston
authors.affiliation: PRA International, Lenexa, KS, USA.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Thompson
authors.affiliation: PRA International, Lenexa, KS, USA.
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Willsie
mesh_terms: D000328:Adult; D000658:Amoxicillin / Q000009:adverse effects / Q000493:pharmacokinetics*; D002939:Ciprofloxacin / Q000009:adverse effects / Q000493:pharmacokinetics*; D003093:Colitis, Ulcerative / Q000188:drug therapy; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D019804:Mesalamine / Q000494:pharmacology*; D008795:Metronidazole / Q000009:adverse effects / Q000493:pharmacokinetics*; D008875:Middle Aged; D013420:Sulfamethoxazole / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D008795:Metronidazole; D019804:Mesalamine; D002939:Ciprofloxacin; D000658:Amoxicillin; D013420:Sulfamethoxazole
keywords: pharmacokinetics; safety; ulcerative colitis