Format

Send to

Choose Destination
Br J Clin Pharmacol. 2015 Nov;80(5):1021-30. doi: 10.1111/bcp.12666. Epub 2015 Jul 6.

Drug disposition and modelling before and after gastric bypass: immediate and controlled-release metoprolol formulations.

Author information

1
Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
2
Centre for Applied Pharmacokinetic Research, School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, UK.
3
Clinical and Experimental Endocrinology, KU Leuven and Department of Endocrinology, University Hospitals Leuven/KU Leuven, Campus Gasthuisberg, Leuven, Belgium.
4
Center for Clinical Pharmacology, University Hospitals Leuven/KU Leuven, Campus Gasthuisberg, Leuven, Belgium.
5
Department of Abdominal Surgery, University Hospitals Leuven/KU Leuven, Campus Gasthuisberg, Leuven, Belgium.

Abstract

AIMS:

The aim of the present study was to evaluate the disposition of metoprolol after oral administration of an immediate and controlled-release formulation before and after Roux-en-Y gastric bypass (RYGB) surgery in the same individuals and to validate a physiologically based pharmacokinetic (PBPK) model for predicting oral bioavailability following RYGB.

METHODS:

A single-dose pharmacokinetic study of metoprolol tartrate 200 mg immediate release and controlled release was performed in 14 volunteers before and 6-8 months after RYGB. The observed data were compared with predicted results from the PBPK modelling and simulation of metoprolol tartrate immediate and controlled-release formulation before and after RYGB.

RESULTS:

After administration of metoprolol immediate and controlled release, no statistically significant difference in the observed area under the curve (AUC(0-24 h)) was shown, although a tendency towards an increased oral exposure could be observed as the AUC(0-24 h) was 32.4% [95% confidence interval (CI) 1.36, 63.5] and 55.9% (95% CI 5.73, 106) higher following RYGB for the immediate and controlled-release formulation, respectively. This could be explained by surgery-related weight loss and a reduced presystemic biotransformation in the proximal gastrointestinal tract. The PBPK values predicted by modelling and simulation were similar to the observed data, confirming its validity.

CONCLUSIONS:

The disposition of metoprolol from an immediate-release and a controlled-release formulation was not significantly altered after RYGB; there was a tendency to an increase, which was also predicted by PBPK modelling and simulation.

KEYWORDS:

Roux-en-Y gastric bypass; controlled release; disposition; formulation; metoprolol; modelling

PMID:
25917170
PMCID:
PMC4631175
DOI:
10.1111/bcp.12666
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center