Document 0122
 DOCN  M9550122
 TI    Human pharmacokinetics and tolerability of L-697,639, a non-nucleoside
       HIV-1 reverse transcriptase inhibitor.
 DT    9505
 AU    Van Hecken A; Depre M; De Lepeleire I; Laskin O; Au T; Woolf E; Yeh KC;
       De Schepper PJ; Department of Pharmacology, University of Leuven, School
       of; Medicine, Belgium.
 SO    Int J Clin Pharmacol Res. 1994;14(2):45-50. Unique Identifier : AIDSLINE
       MED/95137735
 AB    L-697,639, a potent and selective non-nucleoside inhibitor of HIV-1
       reverse transcriptase and HIV-1 replication in vitro, was administered
       to healthy male volunteers to investigate the pharmacokinetics and
       tolerability of single and multiple oral doses. Single doses ranging
       from 25 to 500 mg, and multiple doses of up to 100 mg every 12 h for ten
       days, produced no clinically important adverse events. Dose
       proportionality with respect to AUC was seen over the range of 25-100 mg
       administered as a single dose. Single doses of 200 mg and 500 mg
       resulted in an increase in AUC and Cmax that was less than proportional
       to the increase in dose. The mean Cmax after single doses of 25 and 500
       mg were 0.9 and 5.8 microM respectively. Mean Tmax values ranged from
       1.7-3 h. Mean AUCs (0-48 h) were from 6.05 to 50.3 microM h after doses
       from 25 to 500 mg respectively. After the 500-mg dose less than 0.7%
       appeared unchanged in the urine over 48 hours. During multiple doses,
       steady-state was reached on day 3 and slight accumulation occurred
       (approximately 1.5-fold). L-697,639 was well tolerated for up to ten
       days at doses that resulted in mean steady-state trough concentrations
       that exceed their in-vitro susceptibilities.
 DE    Adult  Benzoxazoles/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/
       *PHARMACOKINETICS  Chromatography, High Pressure Liquid  Double-Blind
       Method  Human  HIV-1/*ENZYMOLOGY  Male  Pyridones/ADMINISTRATION &
       DOSAGE/ADVERSE EFFECTS/  *PHARMACOKINETICS  Reverse
       Transcriptase/*ANTAGONISTS & INHIB  Spectrophotometry, Ultraviolet
       Support, Non-U.S. Gov't  CLINICAL TRIAL  JOURNAL ARTICLE  RANDOMIZED
       CONTROLLED TRIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).