The influence of multiple oral doses of zileuton on the steady-state pharmacokinetics of sulfasalazine and its metabolites, sulfapyridine and N-acetylsulfapyridine.
The effects of zileuton (Abbott-64077) on the pharmacokinetics of sulfasalazine (SASP) and its metabolites, sulfapyridine (SP) and N-acetylsulfapyridine (ASP), were studied in a randomised double-blind placebo-controlled study enrolling 14 healthy male volunteers. All subjects received SASP 1 g every 12 hours for 8 days and zileuton 800mg or placebo administered twice daily from day 4 to day 8 inclusive. Coadministration of zileuton did not significantly affect the area under the plasma concentration-time curve, the maximum (Cmax) or minimum (Cmin) plasma concentration and the time to Cmax of SASP, SP or ASP. Likewise, zileuton did not modify the terminal elimination half-life of SASP. It is concluded that coadministration of zileuton 1.6 g/day has no significant effects on the pharmacokinetics of SASP 2 g/day or its metabolites, SP and ASP.
Awni
W M
WM
Pharmacokinetics and Biopharmaceutics Department, Abbott Laboratories, Abbott Park, Illinois, USA.
Braeckman
R A
RA
Locke
C S
CS
Dubé
L M
LM
Granneman
G R
GR
D000284:Administration, Oral; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004311:Double-Blind Method; D004347:Drug Interactions; D006207:Half-Life; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D013427:Sulfapyridine / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D012460:Sulfasalazine / Q000097:blood / Q000493:pharmacokinetics*
D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D016859:Lipoxygenase Inhibitors; C005377:N-acetylsulfapyridine; D012460:Sulfasalazine; C063449:zileuton; D006918:Hydroxyurea; D013427:Sulfapyridine