Pharmacokinetic Interaction of Anaprazole, Amoxicillin and Clarithromycin after Single-Dose Simultaneous Administration and the Effect of Adding Bismuth on Their Pharmacokinetics in Healthy Male Chinese Subjects.

BACKGROUND AND OBJECTIVE: Helicobacter pylori-positive ulcers are treated with a proton pump inhibitor (PPI) + two antibiotics with/without bismuth. The objective of this study was to investigate the pharmacokinetic interaction of the novel PPI anaprazole, amoxicillin and clarithromycin with/without bismuth. METHODS: This single-centre, randomised, open-label phase 1 pharmacokinetic study included healthy Chinese male participants, comprising two cohorts (cohort 1, 4 × 4 crossover design; cohort 2, 2 × 2 crossover design). In cohort 1, 24 participants received four treatment cycles with a different treatment in each cycle; the washout period between cycles was 9 days. Participants were randomly assigned to one of the following four treatment sequences (1:1:1:1): anaprazole sodium enteric-coated tablet 20 mg monotherapy, amoxicillin 1000 mg monotherapy, clarithromycin 500 mg monotherapy, and a three-drug combination (anaprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg). During each treatment cycle, study drugs were administered twice daily for four consecutive days and once in the morning on the fifth day. Cohort 2 participants were administered a single dose of the three-drug combination and a single dose of a four-drug combination (three-drug combination + bismuth 0.6 g) with a washout period of 11 ± 2 days between treatments. Blood samples were collected for pharmacokinetic analysis. RESULTS: Twenty-nine of 32 enrolled participants (cohort 1, n = 24; cohort 2, n = 8) completed the study. There were no significant differences in exposure or time to reach maximum concentration (Tmax) between each single drug or the three-drug combination (cohort 1) or between the three- and four-drug combinations (cohort 1) for any of the drugs/metabolites. CONCLUSIONS: Dose adjustments for individual drugs are not necessary with combined dosing of anaprazole, amoxicillin, clarithromycin and bismuth.