title: Gastric juice, gastric tissue and blood antibiotic concentrations following omeprazole, amoxicillin and clarithromycin triple therapy.
abstract: BACKGROUND
  Amoxicillin and clarithromycin are key antibiotics in proton pump inhibitor-based Helicobacter pylori eradication therapies.
  
  
  OBJECTIVE
  To study gastric mucus and tissue concentrations and collect basic data about optimal antibacterial doses.
  
  
  METHODS
  Plasma, gastric mucosa and gastric juice antibiotic concentrations were measured following either low- or high-dose amoxicillin (750 or 1000 mg b.i.d.) and clarithromycin (400 or 500 mg b.i.d.) given in combination with omeprazole 20 mg bid to 12 male volunteers in an open crossover design. Gastric juice and mucosal biopsy collection was performed either 2 (n=6) or 6 hours (n=6) after dosing.
  
  
  RESULTS
  Amoxicillin concentrations 2 hours after high dosage were gastric juice > gastric body > antral mucosa > plasma. At 6 hours, plasma and gastric juice concentrations were still above the MIC for amoxicillin-susceptible bacteria but no antibiotic was detectable in mucosa samples. Clarithromycin concentrations after high dosage were gastric juice > mucosa > serum; all above the MIC for clarithromycin-susceptible bacteria at both 2 and 6 hours.
  
  
  CONCLUSIONS
  Both dosage regimens provided effective antibiotic concentrations in gastric juice at 2 hours. After dosing, both antibiotics demonstrated high gastric tissue concentrations via local diffusion while clarithromycin also provided sustained delivery (6 hours) via gastric mucosa penetration.
authors.affiliation: Research Center for Clinical Pharmacology, Center for Basic Research, Kitasato Institute, Tokyo, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nakamura
authors.forename: Robin C
authors.initials: RC
authors.lastname: Spiller
authors.forename: David A
authors.initials: DA
authors.lastname: Barrett
authors.forename: Judata I D
authors.initials: JI
authors.lastname: Wibawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Kumagai
authors.forename: Kanji
authors.initials: K
authors.lastname: Tsuchimoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000658:Amoxicillin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D017291:Clarithromycin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005750:Gastric Juice / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D008297:Male; D009853:Omeprazole / Q000008:administration & dosage* / Q000097:blood
chemical_list: D000658:Amoxicillin; D017291:Clarithromycin; D009853:Omeprazole