TY - JOUR
T1 - Montelukast pharmacokinetics in cystic fibrosis
AU - Graff, Gavin R.
AU - Weber, Allan
AU - Wessler-Starman, Deon
AU - Smith, Arnold L.
N1 - Funding Information:
Supported in part by a Medical School Grant from Merck (SING-US-104-9).
PY - 2003/1/1
Y1 - 2003/1/1
N2 - Objectives: 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-rag 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, 2680.0 ± 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.
AB - Objectives: 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-rag 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, 2680.0 ± 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.
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U2 - 10.1067/mpd.2003.mpd0332
DO - 10.1067/mpd.2003.mpd0332
M3 - Article
C2 - 12520255
AN - SCOPUS:0037239114
SN - 0022-3476
VL - 142
SP - 53
EP - 56
JO - Journal of Pediatrics
JF - Journal of Pediatrics
IS - 1
ER -