Studies on drug interactions between esomeprazole, amoxicillin and clarithromycin in healthy subjects

Hassan-Alin, Mohammed; Andersson, Tommy; Niazi, Mohammad; Liljeblad, Mathias; Persson, Bjorn; Röhss, Kerstin

doi:10.5414/cpp44119

Cited by 17 publications

(12 citation statements)

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“…Co-administration of CLR with proton pump inhibitors (PPIs), such as esomeprazole [171], lansoprazole [151,172–175], omeprazole [176–179], pantoprazole [176], and rabeprazole [180]—a combination commonly prescribed as part of Helicobacter pylori treatment—has been investigated in several studies. A double-blinded RCT in 18 healthy volunteers of different genotype groups of CYP2C19 found an increase of approximately 110% of the AUC and C max of (S) -lansoprazole in extensive metabolizers (EMs) [172].…”

Section: Resultsmentioning

confidence: 99%

“…Another double-blinded randomized cross-over study focused on CLR and omeprazole in 21 humans and found CLR to inhibit omeprazole metabolism, resulting in an increase of AUC of approximately 210% [177]. Also, a 200% increase was found in a randomized cross-over study co-administering esomeprazole and CLR to a group of 26 EMs and PMs [171]. A double-blinded cross-over study in 8 healthy volunteers not only studied co-administration of CLR with omeprazole, but also with pantoprazole, and found that the PK of CLR and pantoprazole remained unchanged.…”

Section: Resultsmentioning

confidence: 99%

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Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

et al. 2011

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Like any other drug, antimicrobial drugs are prone to pharmacokinetic drug interactions. These drug interactions are a major concern in clinical practice as they may have an effect on efficacy and toxicity. This article provides an overview of all published pharmacokinetic studies on drug interactions of the commonly prescribed antimicrobial drugs oxazolidinones, rifamycines, macrolides, fluoroquinolones, and beta-lactams, focusing on systematic research. We describe drug-food and drug-drug interaction studies in humans, affecting antimicrobial drugs as well as concomitantly administered drugs. Since knowledge about mechanisms is of paramount importance for adequate management of drug interactions, the most plausible underlying mechanism of the drug interaction is provided when available. This overview can be used in daily practice to support the management of pharmacokinetic drug interactions of antimicrobial drugs.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

et al. 2011

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“…The synergistic effect of these therapies is related to pharmacokinetic interactions. It has been confirmed that triple therapy increases both the AUC and C max of clarithromycin and its active metabolite 14-OH-clarithromycin [7][8][9] . However, the AUC of omeprazole increased almost 2-fold after concomitant administration of CLR [7] , and the AUC of lansoprazole significantly increased from 3.65 to 4.59 mg·h/L after co-administration of CLR and AMX [8] .…”

Section: Introductionmentioning

confidence: 72%

“…Compared with omeprazole, esomeprazole metabolism is more dependent on CYP3A. One study indicated that clarithromycin decreased the rate of esomeprazole metabolism, which doubled the AUC values, regardless of the CYP2C19 genotype [9] . The pharmacokinetics of rebeprazole, which is metabolized by a non-enzymatic pathway with minor CYP2C19 and CYP3A4 involvement, were not altered by clarithromycin or verapamil (a potent CYP3A inhibitor), irrespective of the CYP2C19 genotype [20] .…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic interactions between ilaprazole and clarithromycin following ilaprazole, clarithromycin and amoxicillin triple therapy

et al. 2012

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Aim: To investigate the drug interactions between ilaprazole, a new proton pump inhibitor, and clarithromycin following ilaprazole, clarithromycin and amoxicillin combination therapy. Methods: Twelve healthy Chinese volunteers were recruited in a randomized, open-label, 3-period crossover study. All subjects were administered ilaprazole (5 mg), clarithromycin (500 mg) or a triple therapy, including ilaprazole (5 mg), clarithromycin (500 mg) and amoxicillin (1 g), twice daily for 6 consecutive days. On the 7th day, the drugs were given once, and blood samples were collected and analyzed using a well-validated HPLC/MS/MS method. Results: Following the triple therapy, the peak concentration (C max ) and the area under the concentration-time curve from 0 h to 12 h (AUC 0→12 ) of ilaprazole were significantly decreased, as compared with the single medication group (C max : 1025.0±319.6 vs 1452.3±324.6 ng/mL; AUC 0→12 : 9777.7±3789.8 vs 11363.1±3442.0 ng· h/mL). Similar changes were found for ilaprazole sulfone (C max : 5.9±0.5 vs 9.3±1.7 ng/mL; AUC 0→12 : 201.4±32.1 vs 277.1±66.2 ng· h/mL). The triple therapy significantly elevated the C max of clarithromycin (3161.5±702.2 vs 2541.9±476.2 ng/mL). Conclusion:The H pylori eradication therapy with clarithromycin, amoxicillin and ilaprazole may cause pharmacokinetic interactions that decrease the amount of ilaprazole and its metabolites and elevate that of clarithromycin.

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“…Clarithromycin is a potent cytochrome P450 (CYP) 3A4 inhibitor, and affects most PPIs (such as omeprazole, lansoprazole, and esomeprazole) that are metabolised by CYP3A4 [ 8 – 10 ]. PPIs may, in turn, alter the metabolism of concomitantly administered antibiotics via either CYP enzyme inhibition or a change in the pH-dependent solubility of the drugs [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic drug interaction and safety after coadministration of clarithromycin, amoxicillin, and ilaprazole: a randomised, open-label, one-way crossover, two parallel sequences study

Jin

Yoo

Park

et al. 2018

Eur J Clin Pharmacol

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PurposeIlaprazole, 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.MethodsA 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.ResultsTwenty-eight subjects completed the study. For ilaprazole, the peak concentration (Cmax) 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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (10.1007/s00228-018-2489-2) contains supplementary material, which is available to authorized users.

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Studies on drug interactions between esomeprazole, amoxicillin and clarithromycin in healthy subjects

Cited by 17 publications

References 0 publications

Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

Pharmacokinetic interactions between ilaprazole and clarithromycin following ilaprazole, clarithromycin and amoxicillin triple therapy

Pharmacokinetic drug interaction and safety after coadministration of clarithromycin, amoxicillin, and ilaprazole: a randomised, open-label, one-way crossover, two parallel sequences study

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