| Title |
The Pharmacokinetics of the CYP3A Substrate Midazolam in Morbidly Obese Patients Before and One Year After Bariatric Surgery
|
|---|---|
| Published in |
Pharmaceutical Research, July 2015
|
| DOI | 10.1007/s11095-015-1752-9 |
| Pubmed ID | |
| Authors |
Margreke J. Brill, Anne van Rongen, Eric P. van Dongen, Bert van Ramshorst, Eric J. Hazebroek, Adam S. Darwich, Amin Rostami-Hodjegan, Catherijne A. Knibbe |
| Abstract |
Bariatric surgery is nowadays commonly applied as treatment for morbid obesity (BMI > 40 kg/m(2)). As information about the effects of this procedure on a drug's pharmacokinetics is limited, we aimed to evaluate the pharmacokinetics of CYP3A probe substrate midazolam after oral and intravenous administration in a cohort of morbidly obese patients that was studied before and 1 year post bariatric surgery. Twenty morbidly obese patients (aged 26-58 years) undergoing bariatric surgery participated in the study of which 18 patients returned 1 year after surgery. At both occasions, patients received 7.5 mg oral and 5 mg intravenous midazolam separated by 160 ± 48 min. Per patient and occasion, a mean of 22 blood samples were collected. Midazolam concentrations were analyzed using population pharmacokinetic modeling. One year after bariatric surgery, systemic clearance of midazolam was higher [0.65 (7%) versus 0.39 (11%) L/min, mean ± RSE (P < 0.01), respectively] and mean oral transit time (MTT) was faster [23 (20%) versus 51 (15%) minutes (P < 0.01)], while oral bioavailability was unchanged (0.54 (9%)). Central and peripheral volumes of distribution were overall lower (P < 0.05). In this cohort study in morbidly obese patients, systemic clearance was 1.7 times higher 1 year after bariatric surgery, which may potentially result from an increase in hepatic CYP3A activity per unit of liver weight. Although MTT was found to be faster, oral bioavailability remained unchanged, which considering the increased systemic clearance implies an increase in the fraction escaping intestinal first pass metabolism. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Netherlands | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 82 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 82 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 15 | 18% |
| Student > Ph. D. Student | 13 | 16% |
| Student > Master | 12 | 15% |
| Student > Doctoral Student | 6 | 7% |
| Researcher | 5 | 6% |
| Other | 13 | 16% |
| Unknown | 18 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 20 | 24% |
| Medicine and Dentistry | 19 | 23% |
| Nursing and Health Professions | 5 | 6% |
| Agricultural and Biological Sciences | 4 | 5% |
| Unspecified | 3 | 4% |
| Other | 6 | 7% |
| Unknown | 25 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 July 2015.
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#18,418,919
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#2,477
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#189,490
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Outputs of similar age from Pharmaceutical Research
#19
of 26 outputs
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