1. Pharmacokinetic drug interaction and safety after coadministration of clarithromycin, amoxicillin, and ilaprazole: a randomised, open-label, one-way crossover, two parallel sequences study.
- Author
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Jin BH, Yoo BW, Park J, Kim JH, Lee JY, Shin JS, and Park MS
- Subjects
- 2-Pyridinylmethylsulfinylbenzimidazoles administration & dosage, 2-Pyridinylmethylsulfinylbenzimidazoles adverse effects, 2-Pyridinylmethylsulfinylbenzimidazoles blood, Adult, Amoxicillin administration & dosage, Amoxicillin adverse effects, Amoxicillin blood, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents adverse effects, Anti-Bacterial Agents blood, Clarithromycin administration & dosage, Clarithromycin adverse effects, Clarithromycin blood, Cross-Over Studies, Drug Interactions, Drug Therapy, Combination, Healthy Volunteers, Helicobacter Infections drug therapy, Helicobacter Infections microbiology, Helicobacter pylori drug effects, Humans, Male, Middle Aged, Patient Safety, Proton Pump Inhibitors administration & dosage, Proton Pump Inhibitors adverse effects, Proton Pump Inhibitors blood, Republic of Korea, Risk Assessment, Young Adult, 2-Pyridinylmethylsulfinylbenzimidazoles pharmacokinetics, Amoxicillin pharmacokinetics, Anti-Bacterial Agents pharmacokinetics, Clarithromycin pharmacokinetics, Proton Pump Inhibitors pharmacokinetics
- Abstract
Purpose: Ilaprazole, the latest proton pump inhibitor, can be used with clarithromycin and amoxicillin as a triple therapy regimen for eradicating Helicobacter pylori. The aim of this study was to evaluate pharmacokinetic drug interactions and safety profiles after coadministration of clarithromycin, amoxicillin, and ilaprazole., Methods: A randomised, open-label, one-way crossover, two parallel sequences study was conducted in 32 healthy subjects. In part 1, the subjects received a single dose of ilaprazole 10 mg in period 1 and clarithromycin 500 mg and amoxicillin 1000 mg twice daily for 6 days in period 2. In part 2, the subjects received clarithromycin 500 mg and amoxicillin 1000 mg once in period 1 and ilaprazole 10 mg twice daily for 6 days in period 2. In both sequences, the three drugs were coadministrated once on day 5 in period 2. Pharmacokinetic evaluations of ilaprazole (part 1), and clarithromycin and amoxicillin (part 2) were conducted., Results: Twenty-eight subjects completed the study. For ilaprazole, the peak concentration (C
max ) slightly decreased from 479 (ilaprazole alone) to 446 ng/mL (triple therapy) [Geometric least square mean ratio (90% confidence interval), 0.93 (0.70-1.22)]. The area under the concentration-time curve from 0 h to the last measurable concentration (AUClast ) slightly increased from 3301 to 3538 μg·h/mL [1.07 (0.85-1.35)]. For clarithromycin, the Cmax slightly decreased from 1.87 to 1.72 μg/mL [0.90 (0.70-1.15)], and AUClast slightly increased from 14.6 to 16.5 μg·h/mL [1.09 (0.87-1.37)]. For amoxicillin, the Cmax slightly decreased from 9.37 to 8.14 μg/mL [0.86 (0.74-1.01)], and AUClast slightly decreased from 27.9 to 26.7 μg·h/mL [0.98 (0.83-1.16)]. These changes in the PK parameters of each drug were not statistically significant., Conclusions: The coadministration of ilaprazole, clarithromycin, and amoxicillin was tolerable and did not cause a significant PK drug interaction. Thus, a triple therapy regimen comprising ilaprazole, clarithromycin, and amoxicillin may be an option for the eradication of H. pylori. Clinicaltrials.gov number: NCT02998437.- Published
- 2018
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