In the case of the majority of studied drugs , an increased absorption rate was observed early after RYGBP .
The effect on systemic exposure allows for a low degree of extrapolation , including between drugs subjected to the same major metabolic and transporter pathways .
Anatomical changes in the gastrointestinal tract and subsequent weight loss may influence drug disposition and thus drug dosing following bariatric surgery .
This review systematic ally examines the effects of bariatric surgery on drug pharmacokinetics , focusing especially on the mechanisms involved in restricting oral bioavailability .
The role of CYP2C and CYP3A in the disposition of 3-keto-desogestrel after administration of desogestrel.
AIMS Our objective was to study in vivo the role of CYP2C and CYP3A4 in the disposition of 3-keto-desogestrel after administration of desogestrel , by using the selective inhibitors fluconazole ( CYP2C ) and itraconazole ( CYP3A4 ) . METHODS This study had a three-way crossover design and included 12 healthy females , the data from 11 of whom were analyzed . In the first ( control ) phase all subjects received a single 150 microg oral dose of desogestrel alone . In the second and third phases subjects received a 4 day pretreatment with either 200 mg fluconazole or 200 mg itraconazole once daily in a r and omized balanced order . Desogestrel was given 1 h after the last dose of the CYP inhibitor . Plasma 3-keto-desogestrel concentrations were determined for up to 72 h post dose . RESULTS Pretreatment with itraconazole for 4 days significantly increased the area under the plasma concentration-time curve ( AUC ) of 3-keto-desogestrel by 72.4 % ( 95 % confidence interval on the difference 12 % , 133 % ; P = 0.024 ) compared with the control phase , whereas fluconazole pretreatment had no significant effect ( 95 % CI on the difference -42 % , 34 % ) . Neither enzyme inhibitor affected significantly the maximum concentration ( 95 % CI on the difference 14 % , 124 % for itraconazole and -23 % , 40 % for fluconazole ) or elimination half-life ( 95 % CI on the difference -42 % , 120 % for itraconazole and -24 % , 61 % for fluconazole ) of 3-keto-desogestrel . CONCLUSIONS According to the present study , the biotransformation of desogestrel to 3-keto-desogestrel did not appear to be mediated by CYP2C9 and CYP2C19 as suggested earlier . However , the further metabolism of 3-keto-desogestrel seems to be catalyzed by CYP3A4
In the case of the majority of studied drugs , an increased absorption rate was observed early after RYGBP .
The effect on systemic exposure allows for a low degree of extrapolation , including between drugs subjected to the same major metabolic and transporter pathways .
Anatomical changes in the gastrointestinal tract and subsequent weight loss may influence drug disposition and thus drug dosing following bariatric surgery .
This review systematic ally examines the effects of bariatric surgery on drug pharmacokinetics , focusing especially on the mechanisms involved in restricting oral bioavailability .