title: Effect of montelukast on single-dose theophylline pharmacokinetics.
abstract: The effect of montelukast (MK-0476), a cysteinyl leukotriene receptor antagonist in development for treatment of asthma, on single-dose theophylline plasma concentrations was studied in three separate clinical trials. Montelukast was evaluated at 10 mg once daily (the clinical dosage), 200 mg once daily, and 600 mg (200 mg three times daily). At the clinical dosage, montelukast did not change single-dose theophylline plasma concentration in a clinically important manner. The geometric mean ratios for theophylline area under the plasma concentration versus time curve (AUC0-->infinity ) (0.92) and maximal plasma concentration (Cmax ) (1.04) were well within the predefined and generally accepted bioequivalence range of 0.80 and 1.25. Montelukast decreased theophylline Cmax by 12% and 10%, AUC0-->infinity by 43% and 44%, and elimination half-time by 44% and 39% at 200 mg/d (oral and intravenous, respectively), and at 600 mg/d, montelukast decreased theophylline Cmax by 25%, AUC0-->infinity by 66%, and elimination half-time by 63%. These results show that montelukast at the clinical dosage did not change theophylline pharmacokinetics in a clinically important manner, but at 20- to 60-fold higher dosages, montelukast significantly reduced the theophylline pharmacokinetics parameters; an apparent dosage dependence is suggested.
authors: Merck Research Laboratories, Departments of Pulmonary-Immunology, Clinical Pharmacology, and Biostatistics, Rahway, NJ, USA.
authors: K
authors: K
authors: Malmstrom
authors: J
authors: J
authors: Schwartz
authors: T F
authors: TF
authors: Reiss
authors: T J
authors: TJ
authors: Sullivan
authors: J H
authors: JH
authors: Reese
authors: L
authors: L
authors: Jauregui
authors: K
authors: K
authors: Miller
authors: M
authors: M
authors: Scott
authors: S
authors: S
authors: Shingo
authors: I
authors: I
authors: Peszek
authors: P
authors: P
authors: Larson
authors: D
authors: D
authors: Ebel
authors: T L
authors: TL
authors: Hunt
authors: R D
authors: RD
authors: Huhn
authors: K
authors: K
authors: Bachmann
mesh_terms: D000085:Acetates / Q000008:administration & dosage* / Q000494:pharmacology*; D000284:Administration, Oral; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003521:Cyclopropanes; D004311:Double-Blind Method; D004347:Drug Interactions; D016903:Drug Monitoring; D006801:Humans; D007275:Injections, Intravenous; D020024:Leukotriene Antagonists / Q000008:administration & dosage* / Q000494:pharmacology*; D008297:Male; D011804:Quinolines / Q000008:administration & dosage* / Q000494:pharmacology*; D013440:Sulfides; D013806:Theophylline / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D000085:Acetates; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D013806:Theophylline; C093875:montelukast