| Title |
Elevated Plasma Moxifloxacin Concentrations and SLCO1B1 g.−11187G>A Polymorphism in Adults with Pulmonary Tuberculosis
|
|---|---|
| Published in |
Antimicrobial Agents and Chemotherapy, April 2018
|
| DOI | 10.1128/aac.01802-17 |
| Pubmed ID | |
| Authors |
Marc Weiner, Jon Gelfond, Teresa L. Johnson-Pais, Melissa Engle, Charles A. Peloquin, John L. Johnson, Erin E. Sizemore, William R. Mac Kenzie |
| Abstract |
Moxifloxacin exhibits concentration-dependent prolongation of human QTc intervals and bactericidal activity againstMycobacterium tuberculosisHowever, moxifloxacin plasma concentrations are variable between patients. We evaluated whether human gene polymorphisms affect moxifloxacin plasma concentrations in tuberculosis patients from two geographic regions. We enrolled a convenience sample of 49 adults with drug-sensitive pulmonary tuberculosis from Africa and the United State s enrolled in two treatment trials of moxifloxacin as part of multidrug therapy. Pharmacokinetic parameters were evaluated by noncompartmental techniques. Human single-nucleotide polymorphisms of transporter genes were evaluated with analysis of covariance on moxifloxacin exposure and peak concentration (Cmax). Moxifloxacin area under the concentration-time curve from 0 to 24 h (AUC0-24) and Cmaxwere significantly increased by drug mg/kg dosage and genotype of variant g.-11187G>A in theSLCO1B1gene (rs4149015), but not by geographic region. Median moxifloxacin AUC0-24was 46% higher and Cmax30% higher in 4 (8% of) participants who had theSLCO1B1g.-11187 AG genotype compared with 45 participants who had the wild type GG genotype (median from model, AUC0-2434.4 vs. 23.6 μg*h/mL,P=.005; Cmax3.5 vs. 2.7 μg/mL,P=.009, ANCOVA). Because moxifloxacin exhibits concentration-dependent prolongation of human QTc intervals, and prolonged QTc intervals are associated with cardiac arrhythmia, further study is needed to evaluate risk associated with theSLCO1B1g.-11187G>A variant. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 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 46 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 46 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Other | 8 | 17% |
| Student > Master | 6 | 13% |
| Student > Bachelor | 5 | 11% |
| Researcher | 4 | 9% |
| Student > Doctoral Student | 2 | 4% |
| Other | 8 | 17% |
| Unknown | 13 | 28% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 9 | 20% |
| Biochemistry, Genetics and Molecular Biology | 8 | 17% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 11% |
| Economics, Econometrics and Finance | 2 | 4% |
| Agricultural and Biological Sciences | 1 | 2% |
| Other | 6 | 13% |
| Unknown | 15 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 16. 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 02 May 2022.
All research outputs
#2,360,991
of 26,017,215 outputs
Outputs from Antimicrobial Agents and Chemotherapy
#1,129
of 15,783 outputs
Outputs of similar age
#47,874
of 343,721 outputs
Outputs of similar age from Antimicrobial Agents and Chemotherapy
#42
of 233 outputs
Altmetric has tracked 26,017,215 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 15,783 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.2. This one has done particularly well, scoring higher than 92% of its peers.
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We're also able to compare this research output to 233 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 81% of its contemporaries.