Pharmacokinetics and bioavailability of montelukast sodium (MK-0476) in healthy young and elderly volunteers.
A study was conducted to (i) characterize the multiple-dose pharmacokinetics of oral montelukast sodium (MK-0476), 10 mg d-1 in healthy young subjects (N = 12), (ii) evaluate the pharmacokinetics of montelukast in healthy elderly subjects (N = 12), and (iii) compare the pharmacokinetics and oral bioavailability of montelukast between elderly and young subjects. Following oral administration of montelukast sodium, 10 mg d-1 (the therapeutic regimen for montelukast sodium) for 7 d, there was little difference in the plasma concentration-time profiles of montelukast in young subjects between day 1 and day 7 dosing. On average, trough plasma concentrations of montelukast were nearly constant, ranging from 18 to 24 ng mL-1 on days 3-7, indicating that the steady state of montelukast was attained on day 2. The mean accumulation ratio was 1.14, indicating that this dose regimen results in a 14% accumulation of montelukast. In elderly subjects, mean values of plasma clearance (Cl), steady-state volume of distribution (Vss), plasma terminal half-life (t1/2), and mean residence time in the body (MRTIV) following a 7 mg intravenous (5 min infusion) administration of montelukast sodium in the elderly were 30.8 mL min-1, 9.7 L, 6.7 h, and 5.4 h, respectively. Following a 10 mg oral dose, the bioavailability of montelukast in healthy elderly averaged 61%, very close to that (62%) determined previously in healthy young subjects. Also following the 10 mg oral administration, the mean values of AUC0-->infinity, Cmax, tmax, and t1/2, and the mean plasma concentration-time profile of montelukast in the elderly, were generally similar to those in young subjects, indicating that age has little or no effect on the pharmacokinetics of montelukast. There is no need to modify dosage as a function of age.
Zhao
J J
JJ
Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA.
Rogers
J D
JD
Holland
S D
SD
Larson
P
P
Amin
R D
RD
Haesen
R
R
Freeman
A
A
Seiberling
M
M
Merz
M
M
Cheng
H
H
D000085:Acetates / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000328:Adult; D000367:Age Factors; D000368:Aged; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003521:Cyclopropanes; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D013440:Sulfides
D000085:Acetates; D003521:Cyclopropanes; D011804:Quinolines; D013440:Sulfides; C093875:montelukast