| Title |
A Model for Predicting the Interindividual Variability of Drug-Drug Interactions
|
|---|---|
| Published in |
The AAPS Journal, December 2016
|
| DOI | 10.1208/s12248-016-0021-0 |
| Pubmed ID | |
| Authors |
M. Tod, L. Bourguignon, N. Bleyzac, S. Goutelle |
| Abstract |
Pharmacokinetic drug-drug interactions are frequently characterized and quantified by an AUC ratio (Rauc). The typical value of the AUC ratio in case of cytochrome-mediated interactions may be predicted by several approaches, based on in vitro or in vivo data. Prediction of the interindividual variability of Rauc would help to anticipate more completely the consequences of a drug-drug interaction. We propose and evaluate a simple approach for predicting the standard deviation (sd) of Ln(Rauc), a metric close to the interindividual coefficient of variation of Rauc. First, a model was derived to link sd(Ln Rauc) with the substrate fraction metabolized by each cytochrome and the potency of the interactors, in case of induction or inhibition. Second, the parameters involved in these equations were estimated by a Bayesian hierarchical model, using the data from 56 interaction studies retrieved from the literature. Third, the model was evaluated by several metrics based on the fold prediction error (PE) of sd(Ln Rauc). The median PE was 0.998 (the ideal value is 1) and the interquartile range was 0.96-1.03. The PE was in the acceptable interval (0.5 to 2) in 52 cases out of 56. Fourth, a surface plot of sd(Ln Rauc) as a function of the characteristics of the substrate and the interactor has been built. The minimal value of sd(Ln Rauc) was about 0.08 (obtained for Rauc = 1) while the maximal value, 0.7, was obtained for interactions involving highly metabolized substrates with strong interactors. |
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 States | 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 10 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 10 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Other | 2 | 20% |
| Researcher | 2 | 20% |
| Student > Ph. D. Student | 1 | 10% |
| Unspecified | 1 | 10% |
| Professor > Associate Professor | 1 | 10% |
| Other | 1 | 10% |
| Unknown | 2 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 30% |
| Medicine and Dentistry | 3 | 30% |
| Agricultural and Biological Sciences | 1 | 10% |
| Unspecified | 1 | 10% |
| Unknown | 2 | 20% |
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 23 April 2017.
All research outputs
#17,887,790
of 22,965,074 outputs
Outputs from The AAPS Journal
#1,050
of 1,293 outputs
Outputs of similar age
#291,795
of 420,255 outputs
Outputs of similar age from The AAPS Journal
#23
of 36 outputs
Altmetric has tracked 22,965,074 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,293 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.0. This one is in the 14th percentile – i.e., 14% of its peers scored the same or lower than it.
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 420,255 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 26th percentile – i.e., 26% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 36 others from the same source and published within six weeks on either side of this one. This one is in the 11th percentile – i.e., 11% of its contemporaries scored the same or lower than it.