PHARMACOKINETICS AND BIOAVAILABILITY OF MONTELUKAST SODIUM (MK-0476) IN HEALTHY-YOUNG AND ELDERLY VOLUNTEERS

A study was conducted to (i) characterize the multiple-dose pharmacoki netics of oral montelukast sodium (MK-0476), 10 mg d(-1) in healthy yo ung subjects (N = 12), (ii) evaluate the pharmacokinetics of monteluka st in healthy elderly subjects (N = 12), and (iii) compare the pharmac okinetics and oral bioavailability of montelukast between elderly and young subjects. Following oral administration of montelukast sodium, 1 0 mg d(-1) (the therapeutic regimen for montelukast sodium) for 7 d, t here was little difference in the plasma concentration-time profiles o f montelukast in young subjects between day 1 and day 7 dosing. On ave rage, trough plasma concentrations of montelukast were nearly constant , ranging from 18 to 24 ng mL(-1) on days 3-7, indicating that the ste ady state of montelukast was attained on day 2. The mean accumulation ratio was 1.14, indicating that this dose regimen results in a 14% acc umulation of montelukast. In elderly subjects, mean values of plasma c learance (Cl), steady-state volume of distribution (V-ss), plasma term inal half-life (t(1/2)), and mean residence time in the body (MRTIV) f ollowing a 7 mg intravenous (5 min infusion) administration of montelu kast 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 AUC(0-infinity), C-max, t( max) and t(1/2), and the mean plasma concentration-time profile of mon telukast in the elderly, were generally similar to those in young subj ects, indicating that age has little or no effect on the pharmacokinet ics of montelukast. There is no need to modify dosage as a function of age. (C) 1997 John Wiley & Sons, Ltd.