Gastric juice, gastric tissue and blood antibiotic concentrations following omeprazole, amoxicillin and clarithromycin triple therapy.
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.
Nakamura
Masahiko
M
Research Center for Clinical Pharmacology, Center for Basic Research, Kitasato Institute, Tokyo, Japan.
Spiller
Robin C
RC
Barrett
David A
DA
Wibawa
Judata I D
JI
Kumagai
Naoki
N
Tsuchimoto
Kanji
K
Tanaka
Takeshi
T
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
D000658:Amoxicillin; D017291:Clarithromycin; D009853:Omeprazole