科研之友
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摘要
Background: Bariatric surgery such as the Roux-en-Y gastric bypass (RYGB) is currently used as a treatment for severe obesity. Alteration of the gastrointestinal tract by this procedure suggests a potential for clinically significant alterations in the bioavailability of ingested medications including antidepressants. Objectives: The purpose of this trial was to determine to what extent the RYGB procedure alters the area under the plasma concentration/time curve (AUC(0-infinity)) of the antidepressant, duloxetine. Methods: Ten subjects who were 1 year post-RYGB where compared with healthy control subjects matched for body mass index, age, and sex. Ultrarapid or poor metabolizers for cytochrome P450 2D6 were excluded from the study. Subjects received a single dose of 60 mg of duloxetine. Nineteen plasma samples were obtained during 72 hours to characterize the plasma level profile. Results: The mean AUC(0-infinity) was significantly smaller for the postbariatric surgery (PBS) group (646.74 ng x h/mL [SD, 79.70; range, 539.57-791.62], P = 0.017) compared to the nonsurgical control group (1119.91 ng x h/mL [SD, 593.40; range, 415.5-2426.56]). The T-max was also significantly shorter for the PBS group (2.2 hours) compared to the nonsurgical control group (6 hours; P = 0.005). No significant difference in C-max or half-life was identified. Conclusions: To our knowledge, this is the first reported study exploring duloxetine pharmacokinetics PBS. This trial found that the bariatric surgery group was exposed to only 57.7% of duloxetine as compared to the nonsurgery group. This finding suggests that clinicians need to monitor patients closely after bariatric surgery and that further exploration of the effects of bariatric surgery on antidepressant pharmacokinetic parameters is warranted.
- 出版日期2013-8
