title: Effect of clarithromycin and fluconazole on the pharmacokinetics of montelukast in human volunteers.
abstract: 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 10 mg montelukast. 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 ( AUC(0-∞)) 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 AUC(0-∞) 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.
authors.affiliation: Department of Clinical Pharmacy, Tanta University, Tanta 8310, Egypt.
authors.forename: Sahar K
authors.initials: SK
authors.lastname: Hegazy
authors.forename: Mokhtar M
authors.initials: MM
authors.lastname: Mabrouk
authors.forename: Alaa E
authors.initials: AE
authors.lastname: Elsisi
authors.forename: Noha O
authors.initials: NO
authors.lastname: Mansour
mesh_terms: D000085:Acetates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000935:Antifungal Agents / Q000008:administration & dosage*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D017291:Clarithromycin / Q000008:administration & dosage*; D018592:Cross-Over Studies; D003521:Cyclopropanes; D065729:Cytochrome P-450 CYP2C9; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004534:Egypt; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D015725:Fluconazole / Q000008:administration & dosage*; D006207:Half-Life; D006801:Humans; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D049990:Membrane Transport Modulators / Q000008:administration & dosage; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D011804:Quinolines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013440:Sulfides
chemical_list: D000085:Acetates; D018927:Anti-Asthmatic Agents; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D003521:Cyclopropanes; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D020024:Leukotriene Antagonists; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D011804:Quinolines; D013440:Sulfides; D015725:Fluconazole; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D017291:Clarithromycin; C093875:montelukast