Evaluation of the impact of waterpipe tobacco smoke exposure on the activity and expression of rat hepatic CYP450: a pharmacokinetic study.

AbstractWaterpipe smoke contains many toxic constituents that can alter drug pharmacokinetics. This study assessed the effect of waterpipe smoke exposure on the activity and expression of CYP450 enzymes in rats. Animals (n = 10/group) were exposed to either waterpipe smoke or side-stream cigarette smoke for 1 h/day (6 days/week) for 31 days, or fresh air (control). An intragastric cocktail solution containing three probe drugs, phenacetin, chlorzoxazone and testosterone was administered to assess the activity of CYP1A2, CYP2E1 and CYP3A, respectively. Serum concentrations were determined using LC-MS/MS and the pharmacokinetic parameters were calculated. The mRNA expression of hepatic enzymes was also quantified. Waterpipe and cigarette smoke exposure did not significantly alter the pharmacokinetics of phenacetin, chlorzoxazone and testosterone. For example, the clearance and drug exposure values were comparable among groups for all probe drugs. Additionally, there was no significant effect of waterpipe an...