Proximal Roux-en-Y gastric bypass alters drug absorption pattern but not systemic exposure of CYP3A4 and P-glycoprotein substrates.
Pharmacotherapy
; 35(4): 361-9, 2015 Apr.
Article
en En
| MEDLINE
| ID: mdl-25757445
ABSTRACT
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:
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 MAINRESULTS:
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 (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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Midazolam
/
Derivación Gástrica
/
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP
/
Digoxina
/
Citocromo P-450 CYP3A
Tipo de estudio:
Observational_studies
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Pharmacotherapy
Año:
2015
Tipo del documento:
Article