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Drug disposition and modelling before and after gastric bypass: immediate and controlled‐release metoprolol formulations
Author(s) -
Gesquiere Ina,
Darwich Adam S.,
Van der Schueren Bart,
Hoon Jan,
Lannoo Matthias,
Matthys Christophe,
Rostami Amin,
Foulon Veerle,
Augustijns Patrick
Publication year - 2015
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12666
Subject(s) - metoprolol , physiologically based pharmacokinetic modelling , metoprolol tartrate , pharmacokinetics , bioavailability , pharmacology , oral administration , disposition , medicine , controlled release , drug , anesthesia , psychology , social psychology
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.