Montelukast pharmacokinetics in cystic fibrosis.
OBJECTIVE
To determine if patients with cystic fibrosis (CF) have an altered pharmacokinetic profile of montelukast, we studied the single-dose pharmacokinetics in 12 patients with CF and 12 age- and gender-matched controls after they received a 10-mg oral dose.


METHODS
Plasma samples were collected before dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours after drug administration. The specimens were analyzed by high-performance liquid chromatography (HPLC).


RESULTS
The mean systemic clearance (mL/min) values (+/- SD) were not statistically different between the CF subjects (55.53 +/- 44.0 mL/min) and the controls (57.12 +/- 18.42 mL/min), nor were the results significantly different when normalized to body surface area or body weight. The mean value for elimination half-life, elimination rate constant, area under the plasma concentration versus time curve, and maximum concentration for controls was 2.37 +/- 0.38 hours, 0.30 +/- 0.05 hours(-1), 2,680.0 +/- 693.6 ng. min/mL, and 448.9 +/- 165.3 ng/mL; and for the CF patients it was 2.97 +/- 1.21 hours, 0.28 +/- 0.13 hrs(-1), 3976.1 +/- 2073.4 ng. min/mL, 606.7 +/- 237.8 ng/mL. There were no statistically significant differences (all P >.05) in the measured pharmacokinetic parameters between the CF and control subjects.


CONCLUSIONS
We conclude that the dose of montelukast and the dosing interval does not need to be modified if the goal is to mimic the serum concentration used to treat asthma. The effectiveness of these concentrations for the inflammatory lung disease of patients with CF is unknown.
Graff
Gavin R
GR
University of Missouri, Department of Child Health and Molecular Microbiology, Columbia, Missouri, USA.
Weber
Allan
A
Wessler-Starman
Deon
D
Smith
Arnold L
AL
D000085:Acetates / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000293:Adolescent; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001249:Asthma / Q000097:blood / Q000188:drug therapy; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D003521:Cyclopropanes; D003550:Cystic Fibrosis / Q000097:blood* / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D020024:Leukotriene Antagonists / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D011804:Quinolines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D013440:Sulfides
D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; C093875:montelukast