Effects of CYP2C19, MDR1, and interleukin 1-B gene variants on the eradication rate of Helicobacter pylori infection by triple therapy with pantoprazole, amoxicillin, and metronidazole

• Published in: European journal of clinical pharmacology Vol. 66; no. 7; pp. 681 - 687
• Main Authors: Gawrońska-Szklarz, Barbara, Siuda, Andrzej, Kurzawski, Mateusz, Bielicki, Dariusz, Marlicz, Wojciech, Droździk, Marek
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.07.2010; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: 2-Pyridinylmethylsulfinylbenzimidazoles - administration & dosage; 2-Pyridinylmethylsulfinylbenzimidazoles - blood; Adult; Aged; Aged, 80 and over; Amoxicillin; Amoxicillin - administration & dosage; Anti-Bacterial Agents - administration & dosage; Antibiotics; Aryl Hydrocarbon Hydroxylases - genetics; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Bacteria; Bacterial diseases; Bacterial diseases of the digestive system and abdomen; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; CYP2C19; Cytochrome P-450 CYP2C19; Drug Therapy, Combination; European Continental Ancestry Group - genetics; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene polymorphism; genetic polymorphism; Genetic Variation; Genetics; Genotype; H. pylori; Helicobacter Infections - drug therapy; Helicobacter Infections - genetics; Helicobacter Infections - microbiology; Helicobacter pylori; Helicobacter pylori - drug effects; High-performance liquid chromatography; Homozygotes; Human bacterial diseases; Humans; Infection; Infectious diseases; Interleukin 1; Interleukin-1beta - genetics; Male; MDR1; MDR1 protein; Medical sciences; Metabolism; Metronidazole; Metronidazole - administration & dosage; Middle Aged; Multivariate analysis; Other diseases. Semiology; Peptic Ulcer - drug therapy; Peptic Ulcer - microbiology; peptic ulcers; Pharmacogenetics; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Poland; Polymerase chain reaction; Polymorphism; Proton Pump Inhibitors - administration & dosage; Proton Pump Inhibitors - blood; Protons; Restriction fragment length polymorphism; Stomach; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Treatment Failure; Ulcers; Poland; Peptic ulcer; MDR1; Pharmacogenetics; CYP2C19; Interleukin-1β; Genetic polymorphism; Antiulcer agent; H. pylori; Proton pump inhibitor; Antiprotozoal agent; Antifungal agent; Antisecretory agent; Intestinal disease; Genetics; Human; β-Lactams; Cytokine; Enzyme inhibitor; Genotype; Interleukin 1β; Infection; Variant; Antibiotic; Amoxicillin; exchanging ATPase; Metronidazole; Nitro compound; Imidazole derivatives; Genetic variability; Isozyme; H; Spirillaceae; K; Eradication; Penicillin derivatives; Gastroduodenal; Helicobacter pylori; Interleukin 1; Bacteria; Gastric disease; Spirillales; Pantoprazole; Enzyme; Cytochrome P450; Treatment; Benzimidazole derivatives; Bacteriosis; MDR-1 gene; Hydrolases; Digestive diseases; Parasiticide; Antibacterial agent; Polymorphism
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-010-0818-1

Objective Eradication of H. pylori is an important treatment strategy in peptic ulcer patients. Current regimens of eradication consist of proton pump inhibitor (PPI) and two antibiotics. Effects of PPI may depend on their metabolism, and other factors important for the pathophysiology of peptic ulcer disease. Aim of the present study was to evaluate an association of CYP2C19, MDR1, and IL-1B polymorphisms with the eradication rate of H. pylori in Polish Caucasian patients treated with a triple therapy of pantoprazole, amoxicillin, and metronidazole. Methods A total of 139 peptic ulcer patients, positive for H. pylori infection, were treated with triple therapy (pantoprazole + amoxicillin + metronidazole). Subsequently, the patients were divided into two groups (group 1, success, and group 2, failure of eradication after therapy) and genotyped by the PCR-RFLP method for the presence of CYP2C19 variant alleles (*2, *3, and *17), and MDR1 3435C>T and IL-1B +3954C>T polymorphisms. Pantoprazole serum concentrations were measured using the HPLC method. Results No significant differences in frequency or distribution of CYP2C19 genotypes were found between the two groups of patients (i.e., with successful H. pylori eradication and treatment failure). However, any carrier of defective CYP2C19*2/*2 genotype was found among patients with treatment failure. Similarly, MDR1 and IL-1B genotypes were found to be significantly associated with the success or failure of H. pylori eradication. Univariate and multivariate analysis of the genotypes did not reveal any significant association between the genotypes and H. pylori eradication. Pantoprazole concentrations differed significantly, and were the highest in patients with defective allele CYP2C19*2 carriers and lowest in hyperactive genotype homozygotes CYP2C19*17/*17. Conclusion The results suggest that the CYP2C19 genotype contrary to MDR1 and IL-1B genotypes may have an impact on the efficacy of H. pylori eradication in peptic ulcer patients treated with pantoprazole in Polish Caucasian peptic ulcer patients administered pantoprazole, amoxicillin, and metronidazole.