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CYP2B6*6, CYP2B6*18, Body weight and sex are predictors of efavirenz pharmacokinetics and treatment response: population pharmacokinetic modeling in an HIV/AIDS and TB cohort in Zimbabwe

Overview of attention for article published in BMC Pharmacology and Toxicology, March 2015
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • One of the highest-scoring outputs from this source (#5 of 250)
  • High Attention Score compared to outputs of the same age (95th percentile)

Mentioned by

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5 news outlets
patent
1 patent

Citations

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56 Dimensions

Readers on

mendeley
115 Mendeley
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Title
CYP2B6*6, CYP2B6*18, Body weight and sex are predictors of efavirenz pharmacokinetics and treatment response: population pharmacokinetic modeling in an HIV/AIDS and TB cohort in Zimbabwe
Published in
BMC Pharmacology and Toxicology, March 2015
DOI 10.1186/s40360-015-0004-2
Pubmed ID
Authors

Milcah Dhoro, Simbarashe Zvada, Bernard Ngara, Charles Nhachi, Gerald Kadzirange, Prosper Chonzi, Collen Masimirembwa

Abstract

Efavirenz (EFV) therapeutic response and toxicity are associated with high inter-individual variability attributed to variation in its pharmacokinetics. Plasma concentrations below 1 μg/ml may result in virologic failure and above 4 μg/ml, may result in central nervous system adverse effects. This study used population pharmacokinetics modeling to explore the influence of demographic and pharmacogenetic factors including efavirenz-rifampicin interaction on EFV pharmacokinetics, towards safer dosing of EFV. Patients receiving an EFV-based regimen for their antiretroviral therapy and a rifampicin-containing anti-TB regimen were recruited. EFV plasma concentrations were measured by HPLC and genomic DNA genotyped for variants in the CYP2B6, CYP2A6 and ABCB1 genes. All patients were evaluated for central nervous system adverse effects characterised as sleep disorders, hallucinations and headaches using the WHO ADR grading system. A pharmacokinetic model was built in a forward and reverse procedure using nonlinear mixed effect modeling in NONMEM VI followed by model-based simulations for optimal doses. CYP2B6*6 and *18 variant alleles, weight and sex were the most significant covariates explaining 55% of inter-individual variability in EFV clearance. Patients with the CYP2B6*6TT genotype had a 63% decrease in EFV clearance despite their CYP2B6*18 genotypes with females having 22% higher clearance compared to males. There was a 21% increase in clearance for every 10 kg increase in weight. The effect of TB/HIV co-treatment versus HIV treatment only was not statistically significant. No clinically relevant association between CYP2B6 genotypes and CNS adverse effects was seen, but patients with CNS adverse effects had a 27% lower clearance compared to those without. Model- based simulations indicated that all carriers of CYP2B6*6 TT genotype would be recommended a dose reduction to 200 mg/day, while the majority of extensive metabolisers may be given 400 mg/day and still maintain therapeutic levels. This study showed that screening for CYP2B6 functional variants has a high predictability for efavirenz plasma levels and could be used in prescribing optimal and safe EFV doses.

Mendeley readers

The data shown below were compiled from readership statistics for 115 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 115 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 26 23%
Student > Ph. D. Student 19 17%
Student > Master 16 14%
Student > Bachelor 10 9%
Student > Postgraduate 7 6%
Other 17 15%
Unknown 20 17%
Readers by discipline Count As %
Medicine and Dentistry 31 27%
Biochemistry, Genetics and Molecular Biology 13 11%
Pharmacology, Toxicology and Pharmaceutical Science 10 9%
Immunology and Microbiology 8 7%
Agricultural and Biological Sciences 6 5%
Other 17 15%
Unknown 30 26%

Attention Score in Context

This research output has an Altmetric Attention Score of 40. 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 January 2018.
All research outputs
#358,420
of 12,400,381 outputs
Outputs from BMC Pharmacology and Toxicology
#5
of 250 outputs
Outputs of similar age
#9,318
of 224,560 outputs
Outputs of similar age from BMC Pharmacology and Toxicology
#1
of 3 outputs
Altmetric has tracked 12,400,381 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 250 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.4. This one has done particularly well, scoring higher than 98% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 224,560 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 95% of its contemporaries.
We're also able to compare this research output to 3 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them