Pharmacokinetics and bioavailability of montelukast sodium (MK-0476) in healthy young and elderly volunteers

✍ Scribed by Jamie J. Zhao; J. Douglas Rogers; Sherry D. Holland; Patrick Larson; Raju D. Amin; Rita Haesen; Amanda Freeman; M. Seiberling; M. Merz; Haiyung Cheng

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 140 KB
• Volume: 18
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/(sici)1099-081x(199712)18:9<769::aid-bdd60>3.0.co;2-k

✦ Synopsis

A study was conducted to (i) characterize the multiple-dose pharmacokinetics of oral montelukast sodium (MK-0476), 10 mg d 71 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 71 (the therapeutic regimen for montelukast sodium) for 7 d, there was little dierence in the plasma concentration±time pro®les 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 71 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 (V ss ), plasma terminal half-life (t 1a2 ), and mean residence time in the body (MRT IV ) following a 7 mg intravenous (5 min infusion) administration of montelukast sodium in the elderly were 30´8 mL min 71 , 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 03I , C max , t max , and t 1a2 , and the mean plasma concentration±time pro®le of montelukast in the elderly, were generally similar to those in young subjects, indicating that age has little or no eect on the pharmacokinetics of montelukast. There is no need to modify dosage as a function of age. &1997 John Wiley & Sons, Ltd.