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 .
Pharmacokinetic assessment of a five-probe cocktail for CYPs 1A2, 2C9, 2C19, 2D6 and 3A.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Numerous cocktails using concurrent administration of several cytochrome P450 ( CYP ) isoform-selective probe drugs have been reported to investigate drug-drug interactions in vivo . * This approach has several advantages : characterize the inhibitory or induction potential of compounds in development toward the CYP enzymes identified in vitro in an in vivo situation , assess several enzymes in the same trial , and have complete in vivo information about potential CYP-based drug interactions . WHAT THIS STUDY ADDS * This study describes a new cocktail containing five probe drugs that has never been published . * This cocktail can be used to test the effects of a new chemical entity on multiple CYP isoforms in a single clinical study : CYP1A2 ( caffeine ) , CYP2C9 ( warfarin ) , CYP2C19 ( omeprazole ) , CYP2D6 ( metoprolol ) , and CYP3A ( midazolam ) and was design ed to overcome potential liabilities of other reported cocktails . AIMS To assess the pharmacokinetics ( PK ) of selective substrates of CYP1A2 ( caffeine ) , CYP2C9 ( S-warfarin ) , CYP2C19 ( omeprazole ) , CYP2D6 ( metoprolol ) and CYP3A ( midazolam ) when administered orally and concurrently as a cocktail relative to the drugs administered alone . METHODS This was an open-label , single-dose , r and omized , six-treatment six-period six-sequence William 's design study with a wash-out of 7 or 14 days . Thirty healthy male subjects received 100 mg caffeine , 100 mg metoprolol , 0.03 mg kg(-1 ) midazolam , 20 mg omeprazole and 10 mg warfarin individually and in combination ( cocktail ) . Poor metabolizers of CYP2C9 , 2C19 and 2D6 were excluded . Plasma sample s were obtained up to 48 h for caffeine , metoprolol and omeprazole , 12 h for midazolam , 312 h for warfarin and the cocktail . Three different vali date d liquid chromatography t and em mass spectrometry methods were used . Noncompartmental PK parameters were calculated . Log-transformed C(max ) , AUC(last ) and AUC for each analyte were analysed with a linear mixed effects model with fixed term for treatment , sequence and period , and r and om term for subject within sequence . Point estimates ( 90 % CI ) for treatment ratios ( individual/cocktail ) were computed for each analyte C(max ) , AUC(last ) and AUC . RESULTS There was no PK interaction between the probe drugs when administered in combination as a cocktail , relative to the probes administered alone , as the 90 % CI of the PK parameters was within the prespecified bioequivalence limits of 0.80 , 1.25 . CONCLUSION The lack of interaction between probes indicates that this cocktail could be used to evaluate the potential for multiple drug-drug interactions in vivo
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 .