ArticleClinical pharmacokinetics2021
Effect of Ponesimod Exposure on Total Lymphocyte Dynamics in Patients with Multiple Sclerosis.
Article in Clinical pharmacokinetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
3 citing papers in PubMed, 6 citations in OpenAlex.
- An exposure-response analysis of ponesimod clinical efficacy in a randomized phase III study in patients with relapsing multiple sclerosis.CPT: pharmacometrics & systems pharmacology · 2022Trial
- Clinical Pharmacokinetics of Ponesimod, a Selective S1P1 Receptor Modulator, in the Treatment of Multiple Sclerosis.Clinical pharmacokinetics · 2023Review
- The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination.Multiple sclerosis and related disorders · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe aim of this study was to characterize the relationship between ponesimod plasma concentrations and the temporal evolution of lymphocyte counts in multiple sclerosis (MS) patients.
methodsPopulation pharmacokinetic (PK) and PK/pharmacodynamic (PD) models were developed using data from phase I, II, and III trials, and the impact of clinically relevant covariates on PK and PD parameters was assessed. Simulations were conducted to evaluate the maximal lymphocyte count reduction after ponesimod treatment, and the time required for total lymphocyte counts to return to normal values after treatment interruption.
resultsIn MS patients, ponesimod PK were characterized by a low mean apparent plasma clearance (5.52 L/h) and a moderate mean apparent volume of distribution at steady state (239 L). The model developed indicated that none of the evaluated covariates (age, sex, formulation, food, body weight, clinical condition, and renal impairment) had a clinically relevant impact on the PK/PD parameters. In MS patients, total lymphocyte counts were characterized by a maximum reduction of 88.0% and a half maximal inhibitory concentration (IC
conclusionsThe population PK/PD model well-characterized the PK of ponesimod and the time course of total lymphocyte counts in MS patients. Additionally, none of the evaluated covariates had a clinically relevant impact. This should be taken into consideration when assessing the risk of infection, administration of live-attenuated vaccines, and concomitant use of immunosuppressants.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.