| Title |
Population pharmacokinetics and pharmacodynamics of ponesimod, a selective S1P1 receptor modulator
|
|---|---|
| Published in |
Journal of Pharmacokinetics and Pharmacodynamics, June 2014
|
| DOI | 10.1007/s10928-014-9362-4 |
| Pubmed ID | |
| Authors |
Andreas Krause, Patrick Brossard, Daniele D’Ambrosio, Jasper Dingemanse |
| Abstract |
Ponesimod (ACT-128800), a reversible, orally active, selective S1P1 receptor modulator, prevents the egress of lymphocytes from the lymph node into the systemic circulation. It is currently in clinical development for the treatment of relapsing multiple sclerosis. Modulation of circulating lymphocytes serves as biomarker of efficacy and safety, such that the quantitative characterization of the pharmacokinetic/pharmacodynamic (PK/PD) relationship guides the clinical development of the compound. The availability of a variety of doses, dosing regimens, and treatment durations permitted estimation of the pharmacokinetics characterized by an absorption lag time followed by a sequential zero/first-order absorption and two compartments with first-order elimination. The PD are modeled as an indirect-effect model with rates of appearance and disappearance of lymphocytes in blood with a circadian rhythm and a drug effect on the rate of appearance. The model suggests a circadian variation of 9 % and a maximum inhibition of 86 % of total lymphocyte count with high doses at steady state. It was instrumental for the selection of doses for subsequent studies that confirmed the effect plateau in total lymphocyte count at approximately 0.5 × 10(9) counts/L. |
Mendeley readers
The data shown below were compiled from readership statistics for 30 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | 3% |
| Brazil | 1 | 3% |
| Unknown | 28 | 93% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 7 | 23% |
| Researcher | 6 | 20% |
| Student > Bachelor | 4 | 13% |
| Student > Master | 4 | 13% |
| Student > Doctoral Student | 2 | 7% |
| Other | 4 | 13% |
| Unknown | 3 | 10% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 7 | 23% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 13% |
| Neuroscience | 4 | 13% |
| Nursing and Health Professions | 2 | 7% |
| Social Sciences | 2 | 7% |
| Other | 6 | 20% |
| Unknown | 5 | 17% |
Attention Score in Context
This research output has an Altmetric Attention Score of 10. 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 09 April 2024.
All research outputs
#3,702,130
of 25,374,647 outputs
Outputs from Journal of Pharmacokinetics and Pharmacodynamics
#29
of 477 outputs
Outputs of similar age
#35,572
of 242,888 outputs
Outputs of similar age from Journal of Pharmacokinetics and Pharmacodynamics
#1
of 4 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 477 research outputs from this source. They receive a mean Attention Score of 4.3. This one has done particularly well, scoring higher than 93% 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 242,888 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 85% of its contemporaries.
We're also able to compare this research output to 4 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