In:
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, Wiley, Vol. 35, No. 4 ( 2015-04), p. 361-369
Abstract:
To evaluate the effect of Roux‐en‐Y gastric bypass surgery ( RYGB ) on the pharmacokinetics of midazolam (a CYP 3A4 substrate) and digoxin (a P‐glycoprotein substrate). Design Prospective, nonblinded, longitudinal, single‐dose pharmacokinetic study in three phases: presurgery baseline and postoperative assessments at 3 and 12 months. Patients Twelve obese patients meeting current standards 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 samples 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 (C max ) 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 (T max ) was reduced by 50%. The mean C max 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 T max 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 C max of a CYP 3A4 substrate with a high extraction ratio was substantially increased after RYGB .
Type of Medium:
Online Resource
ISSN:
0277-0008
,
1875-9114
DOI:
10.1002/phar.2015.35.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2061167-5
SSG:
15,3
