Effect of clarithromycin and fluconazole on the pharmacokinetics of montelukast in human volunteers
European Journal of Clinical Pharmacology, ISSN: 0031-6970, Vol: 68, Issue: 9, Page: 1275-1280
2012
- 13Citations
- 27Captures
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Metrics Details
- Citations13
- Citation Indexes13
- 13
- CrossRef8
- Captures27
- Readers27
- 27
Article Description
Objective Montelukast, a leukotriene receptor antagonist, is used in the treatment of asthma. The objective of the study reported here was to determine whether multiple doses of clarithromycin or fluconazole affect the pharmacokinetics of montelukast. Methods This was a four-phase cross-over study with a washout period of 2 weeks between phases. In phase 1, 12 volunteers received a single oral dose of 10mgmontelukast. In phase 2, the volunteers received a single, oral dose of 1,000 mg clarithromycin once daily for 2 days, followed by, on day 3, a single oral dose of 10 mg montelukast co-administered with clarithromycin. In phase 3, a single oral dose of 50 mg fluconazole was given once daily for 6 days, followed by, on day 7, a single oral dose of 10 mg montelukast co-administered with 50 mg fluconazole. In the last phase (phase 4), a single oral dose of 150 mg fluconazole was given once daily for 6 days, followed by, on day 7, a single oral dose of 10 mg montelukast co-administered with 150 mg fluconazole. The plasma concentration of montelukast was measured by high performance liquid chromatography for 24 h. Results Following clarithromycin co-administration, the area under the concentration time curve from zero to infinity ( AUC0) of montelukast increased by 144% 90%confidence interval (CI) 2.03-2.86]. The co-administration of a single oral dose of 150 and 50 mg fluconazole decreased the montelukast AUC0 by 30.7 (90% CI 0.53-0.81) and 38.8% (90% CI 0.57-0.69), respectively. Conclusions Clarithromycin increased the plasma concentrations of montelukast whereas fluconazole reduced the plasma concentrations of montelukast. The mechanism of the interaction is probably due to interference of the interacting drugs with transporters mediating the uptake of montelukast. © Springer-Verlag 2012.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84866620289&origin=inward; http://dx.doi.org/10.1007/s00228-012-1239-0; http://www.ncbi.nlm.nih.gov/pubmed/22392555; http://link.springer.com/10.1007/s00228-012-1239-0; https://dx.doi.org/10.1007/s00228-012-1239-0; https://link.springer.com/article/10.1007/s00228-012-1239-0; http://www.springerlink.com/index/10.1007/s00228-012-1239-0; http://www.springerlink.com/index/pdf/10.1007/s00228-012-1239-0
Springer Science and Business Media LLC
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