title: Effect of cigarette smoke on pharmacokinetics of oral, intrarectal, or intravenous indomethacin in rats.
abstract: The effect of cigarette smoke exposure on the pharmacokinetics of indomethacin administered orally, intravenously or intrarectally was investigated in rats. When cigarette smoke exposure was performed for 10 min using a Hamburg II smoking machine immediately after the oral administration of indomethacin (5 mg/kg), the plasma indomethacin concentration was significantly lowered during the first 2 h after administration. However, there was no significant difference in plasma indomethacin concentration between the cigarette smoke-exposed and nonexposed control rats thereafter. Cigarette smoke exposure caused a significant decrease in the area under the concentration-time curve from 0 to 4 h (AUC0-4) and a prolongation of the time to reach the maximum concentration (tmax). The plasma level of O-desmethyl-indomethacin (a major metabolite) was not significantly changed by cigarette smoke. When indomethacin (5 mg/kg) was administered to rats intravenously or intrarectally, cigarette smoke exposure did not have any influence on the pharmacokinetics of indomethacin or 0-desmethyl-indomethacin. The pharmacokinetic effect of cigarette smoke on orally administered indomethacin was mimicked by the subcutaneous injection of nicotine at 0.3 mg/kg but not at 0.1 mg/kg. These results suggest that acute exposure to cigarette smoke decreases the plasma concentration of indomethacin when it is administered orally but not intrarectally or intravenously.
authors.affiliation: Department of Pharmacology, Okayama University Medical School, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
authors.forename: Y
authors.initials: Y
authors.lastname: Gomita
authors.forename: R
authors.initials: R
authors.lastname: Oishi
mesh_terms: D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D007213:Indomethacin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012907:Smoking / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
chemical_list: C034674:5-hydroxyindomethacin; D007213:Indomethacin