Single dose and steady-state pharmacokinetics of adinazolam after oral administration to man

✍ Scribed by Dr. John G. Wagner; Mark C. Rogge; Ronald B. Natale; Kenneth S. Albert; Gregory J. Szpunar

• Publisher: John Wiley and Sons
• Year: 1987
• Tongue: English
• Weight: 837 KB
• Volume: 8
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510080502

✦ Synopsis

An aqueous solution containing 1 mg of adinazolam mesylate per ml was administered orally as a single dose (40mg) and with loading doses followed by hourly doses such that final dose rates of 1, 2, and 3mgh-' were administered to steady-state. Four subjects exhibited linear steady-state kinetics, while the other four exhibited Michaelis-Menten kinetics, based on measurement by HPLC of both unchanged drug and the major N-demethyl metabolite. The drug is very rapidly absorbed and has an intrinsic clearance of total (bound + free) drug which averaged 2.141 m i -' based on the steady-state data and 1.171 min-' based on the single dose data, but these means do not differ significantly. The apparent metabolite clearance, CLC,ifm (where fm = fraction of adinazolam converted to the N-demethyl metabolite), averaged 0.170 I min-' based on steady-state data and 0.179 1 min-' based on single dose data and these means d o not differ significantly. Pharmacokinetic parameters, such as these clearances, had large intersubject variations. Three types of bioavailabilities were estimated from the data.