The influence of modulation of @entity38471 and/or cytochrome P450 3A on the pharmacokinetics and pharmacodynamics of orally administered XXXX in @entity235 .

@entity235 @entity3102 @entity38471 @entity33483 @entity1286 @entity1215 @entity28469
The influence of pretreatment with @entity3102 [cytochrome P450 3A (CYP3A) + @entity38471 ( @entity38471 ) inhibitor], @entity28469 (selective @entity38471 inhibitor) and @entity1215 (CYP3A + @entity38471 inducer) on oral @entity1286 pharmacokinetics and pharmacodynamics was investigated in experimental @entity235 . Seven beagles were used in a four-way crossover design. @entity33483 was administered orally (2.5 mg/kg) alone (control group CON) or after pretreatment with @entity3102 (group KETO), @entity28469 (group ELA) or @entity1215 (group RIF). @entity1286 plasma concentrations were analysed by liquid chromatography-tandem mass spectrometry. Sedation scores (none, mild, moderate or severe) were evaluated subjectively. @entity235 were significantly (P < 0.05) more sedated after @entity3102 pretreatment. There were no significant differences between group CON and the other pretreatment groups in pharmacokinetic parameters taking both sexes into account. Sex differences were apparent in some pharmacokinetic parameters of @entity1286 . The area under the plasma concentration time curve (AUC(0-   ) ) was significantly higher, and the total body clearance was significantly lower in male compared to female @entity235 in all treatment groups. @entity3102 , @entity1215 and @entity28469 pretreatment had no significant effects on @entity1286 pharmacokinetics, although @entity235 in the @entity3102 group showed higher sedation scores.
