Studies on drug interactions between esomeprazole, amoxicillin and clarithromycin in healthy subjects.
OBJECTIVE
A combination of esomeprazole, amoxicillin and clarithromycin may be used for Helicobacter pylori eradication. We explored the potential for interactions between these drugs.


METHODS
In 2 randomized, 4-way crossover studies, healthy CYP2C19 extensive metabolizers (EMs) received esomeprazole 40 mg once daily (n = 20) or 20 mg twice daily (b.i.d.) (n = 20), clarithromycin 500 mg b.i.d., amoxicillin 1 g b.i.d. or the combination of the 3 drugs for 7 days. In a third randomized, 2-way, crossover study, 6 healthy CYP2C 19 poor metabolizers (PMs) received esomeprazole 40 mg once daily with and without clarithromycin 500 mg b.i.d. for 1 week.


RESULTS
Triple therapy with esomeprazole 40 mg increased the area under the plasma concentration-time curve during the dosing interval (AUCtau) from 13.31 micromol x h/l (11.12-15.93) for esomeprazole alone to 22.69 micromol x h/l (18.94-27.17) for triple treatment. Respective AUCtau values with esomeprazole 20 mg b.i.d. were 4.97 micromol.h/l (3.97-6.21) and 11.29 micromol x h/l (9.03-14.12). Clarithromycin and amoxicillin plasma levels were largely unchanged by combination therapy. In PMs, the esomeprazole AUC also approximately doubled when administered in combination with clarithromycin. All treatments were well tolerated.


CONCLUSIONS
Clarithromycin decreases the metabolism rate of esomeprazole, leading to approximately doubled AUC values, both in EMs and PMs.
Clinical Pharmacology, AstraZeneca Research and Development, Mölndal, Sweden. mohammed.hassan-alin@astrazeneca.com
M
M
Hassan-Alin
T
T
Andersson
M
M
Niazi
M
M
Liljeblad
B A
BA
Persson
K
K
Röhss
D000328:Adult; D000658:Amoxicillin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D017291:Clarithromycin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19; D004336:Drug Antagonism; D064098:Esomeprazole / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D006207:Half-Life; D016481:Helicobacter Infections / Q000188:drug therapy; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism
D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D000658:Amoxicillin; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D017291:Clarithromycin; D064098:Esomeprazole