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 .
Proximal Roux-en-Y gastric bypass alters drug absorption pattern but not systemic exposure of CYP3A4 and P-glycoprotein substrates.
STUDY OBJECTIVES To evaluate the effect of  Roux-en-Y gastric bypass surgery ( RYGB ) on the pharmacokinetics of midazolam ( a CYP3A4 substrate ) and digoxin ( a P-glycoprotein substrate ) . DESIGN Prospect i ve , nonblinded , longitudinal , single-dose pharmacokinetic study in three phases : presurgery baseline and postoperative assessment s at 3 and 12 months . PATIENTS Twelve obese patients meeting current st and ards for bariatric surgery . MEASUREMENTS AND MAIN RESULTS At each study visit , patients received a single dose of oral digoxin and midazolam at 8 a.m. Blood sample s were collected at regular intervals for 24 hours after dosing . Continuous 12-lead electrocardiogram ( EKG ) , heart rate , blood pressure , and respiratory rate were monitored , and pharmacokinetic parameters from the three visits were compared . The peak plasma concentration ( Cmax ) of midazolam increased by 66 % and 71 % at 3- and 12-month post-RYGB ( p=0.017 and p=0.001 , respectively ) , whereas the median time to peak concentration ( Tmax ) was reduced by 50 % . The mean Cmax for 1'-hydroxymidazolam increased by 87 % and 80 % at 3 and 12 months ( p=0.001 and p<0.001 , respectively ) . However , neither the area under the concentration-time curve ( AUC ) for midazolam nor the metabolite-to-parent AUC ratio changed significantly over time . For digoxin , the median Tmax decreased from 40 minutes at baseline to 30 and 20 minutes at 3 and 12 months , respectively . The mean AUC for digoxin , heart rate , and EKG patterns were similar across the three study phases . CONCLUSION Contemporary proximal RYGB increases the rate of drug absorption without significantly changing the overall exposure to midazolam and digoxin . The Cmax of a CYP3A4 substrate with a high extraction ratio was substantially increased after RYGB
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 .