ArticleClinical pharmacokinetics2023
Population Pharmacokinetics and Pharmacodynamics of Crizanlizumab in Healthy Subjects and Patients with Sickle Cell Disease.
Article in Clinical pharmacokinetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 1 paper.
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.
A Phase II, Multicenter, Randomized, Placebo-Controlled, Double-Blind, 12-Month Study to Assess Safety and Efficacy of SelG1 With or Without Hydroxyurea Therapy in Sickle Cell Disease Patients With Sickle Cell-Related Pain Crises
A Phase 2, Multicenter, Open-Label Study to Assess PK/PD of SEG101 (Crizanlizumab), With or Without Hydroxyurea/Hydroxycarbamide, in Sickle Cell Patients With Vaso-Occlusive Crisis
Who cites it
1 citing paper in PubMed, 3 citations in OpenAlex.
- Trends in surface plasmon resonance biosensing: materials, methods, and machine learning.Analytical and bioanalytical chemistry · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesCrizanlizumab is a humanized monoclonal antibody against P-selectin for the prevention of vaso-occlusive crises in sickle cell disease (SCD). The objective of this study was to investigate crizanlizumab population pharmacokinetics (PK) and pharmacodynamics (PD), as well as influential covariates.
methodsA population PK model for crizanlizumab was developed from healthy volunteer and SCD patient data, using a two-compartment intravenous infusion model utilizing a target-mediated drug disposition (TMDD) approach. The relationship between crizanlizumab concentration and ex vivo P-selectin inhibition was fitted to a non-linear sigmoidal Emax model. Covariate selection was performed in a stepwise manner.
resultsCrizanlizumab exhibits nonlinear pharmacokinetics in the wide dose range of 0.2-8 mg/kg body weight. The population pharmacokinetic base model incorporated body weight as covariate in the form of allometric scaling wherein the exponents were fixed to 0.8. SCD patients had higher baseline soluble P-selectin concentration, resulting in a higher estimated initial target concentration. The typical individual in the model is a 70 kg SCD patient with normal renal function and a baseline albumin of 43 g/L; CL was 0.012 L/h while V
conclusionsRenal and hepatic impairments, concomitant hydroxyurea usage, and presence of anti-drug antibody are not expected to impact the exposure of crizanlizumab. The model allows for extrapolating the PK of crizanlizumab to pediatric population and evaluation of alternative regimens and route of administration. TRIAL REGISTRATION NUMBER [DATE OF REGISTRATION]: SUSTAIN (CSEG101A2201 Phase 2), ClinicalTrials.gov identifier: NCT01895361 [10 July 2013]; CSEG101A2202 (Phase 2), ClinicalTrials.gov identifier: NCT03264989 [29 August 2017].
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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.