| Title |
Higher Midazolam Clearance in Obese Adolescents Compared with Morbidly Obese Adults
|
|---|---|
| Published in |
Clinical Pharmacokinetics, August 2017
|
| DOI | 10.1007/s40262-017-0579-4 |
| Pubmed ID | |
| Authors |
Anne van Rongen, Margreke J. E. Brill, Janelle D. Vaughns, Pyry A. J. Välitalo, Eric P. A. van Dongen, Bert van Ramshorst, Jeffrey S. Barrett, Johannes N. van den Anker, Catherijne A. J. Knibbe |
| Abstract |
The clearance of cytochrome P450 (CYP) 3A substrates is reported to be reduced with lower age, inflammation and obesity. As it is unknown what the overall influence is of these factors in the case of obese adolescents vs. morbidly obese adults, we studied covariates influencing the clearance of the CYP3A substrate midazolam in a combined analysis of data from obese adolescents and morbidly obese adults. Data from 19 obese adolescents [102.7 kg (62-149.5 kg)] and 20 morbidly obese adults [144 kg (112-186 kg)] receiving intravenous midazolam were analysed, using population pharmacokinetic modelling (NONMEM 7.2). In the covariate analysis, the influence of study group, age, total body weight (TBW), developmental weight (WTfor age and length) and excess body weight (WTexcess = TBW - WTfor age and length) was evaluated. The population mean midazolam clearance was significantly higher in obese adolescents than in morbidly obese adults [0.71 (7%) vs. 0.44 (11%) L/min; p < 0.01]. Moreover, clearance in obese adolescents increased with TBW (p < 0.01), which seemed mainly explained by WTexcess, and for which a so-called 'excess weight' model scaling WTfor age and length to the power of 0.75 and a separate function for WTexcess was proposed. We hypothesise that higher midazolam clearance in obese adolescents is explained by less obesity-induced suppression of CYP3A activity, while the increase with WTexcess is explained by increased liver blood flow. The approach characterising the influence of obesity in the paediatric population we propose here may be of value for use in future studies in obese adolescents. |
X Demographics
The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 2 | 40% |
| Netherlands | 1 | 20% |
| Unknown | 2 | 40% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 38 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 8 | 21% |
| Student > Master | 7 | 18% |
| Student > Bachelor | 6 | 16% |
| Librarian | 4 | 11% |
| Student > Ph. D. Student | 3 | 8% |
| Other | 6 | 16% |
| Unknown | 4 | 11% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 11 | 29% |
| Pharmacology, Toxicology and Pharmaceutical Science | 7 | 18% |
| Biochemistry, Genetics and Molecular Biology | 3 | 8% |
| Nursing and Health Professions | 3 | 8% |
| Unspecified | 1 | 3% |
| Other | 3 | 8% |
| Unknown | 10 | 26% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. 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 23 September 2017.
All research outputs
#13,053,501
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Outputs from Clinical Pharmacokinetics
#1,069
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Outputs of similar age
#150,369
of 317,747 outputs
Outputs of similar age from Clinical Pharmacokinetics
#12
of 23 outputs
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