Is a long-term ranitidine-based triple therapy against Helicobacter pylori only a heritage of the past? A prospective, randomized clinicopharmacological study.
BACKGROUND
Acid suppression plus two antibiotics is currently considered the gold standard anti-Helicobacter pylori treatment, but the effective role of gastric antisecretory drugs is still poorly understood.


OBJECTIVE
To compare a 14-day ranitidine-based triple regimen against Helicobacter pylori with one based on omeprazole, and to study the influence of antisecretory drugs on metronidazole pharmacokinetics in human plasma.


METHODS
A total of 150 dyspeptic H. pylori-infected patients were randomized for ranitidine 300 mg b.d. (RCM group) or omeprazole 20 mg b.d. (OCM group) 14-day triple therapy, with clarithromycin 500 mg b.d. and metronidazole 500 mg b.d. On the eighth day of therapy, metronidazole pharmacokinetics was studied in plasma by high-performance liquid chromatography. The pharmacokinetic parameters (terminal half-life, area under the curve, peak-plasma level, peak time) of metronidazole were computed using standard non-compartmental methods. H. pylori status was monitored before and 4 weeks after the end of therapy by histology, serology and rapid urease test.


RESULTS
On an intention-to-treat basis, eradication rates were 91 and 76% for the RCM and OCM groups respectively (P < 0.02). Significantly different pharmacokinetic parameters of metronidazole were found between the groups: peak-plasma level (P < 0.01) and area under the curve (P < 0.02).


CONCLUSIONS
Our results show that the RCM regimen was more effective than that based on OCM and that the antisecretory drugs affected metronidazole availability, increasing the efficacy of ranitidine-based regimens.
Pellegrini
M
M
Digestive Surgery Unit, Department of Surgery and Surgical Specialities, University of Siena, Italy.
Urso
R
R
Giorgi
G
G
Bayeli
P F
PF
Marzocca
G
G
Cerretani
D
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D000897:Anti-Ulcer Agents / Q000008:administration & dosage*; D002851:Chromatography, High Pressure Liquid; D017291:Clarithromycin / Q000008:administration & dosage; D004359:Drug Therapy, Combination / Q000008:administration & dosage; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000378:metabolism; D016480:Helicobacter pylori; D006801:Humans; D008134:Long-Term Care; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage / Q000493:pharmacokinetics; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage*; D011446:Prospective Studies; D011899:Ranitidine / Q000008:administration & dosage*; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000897:Anti-Ulcer Agents; D008795:Metronidazole; D011899:Ranitidine; D017291:Clarithromycin; D009853:Omeprazole