Trial reportClinical pharmacokinetics2014
Population pharmacokinetics of daclizumab high-yield process in healthy volunteers: integrated analysis of intravenous and subcutaneous, single- and multiple-dose administration.
Trial report in Clinical pharmacokinetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Meta-Analysis of Interleukin-2 Receptor Antagonists as the Treatment for Steroid-Refractory Acute Graft-Frontiers in immunology · 2021Pooled it
- Population Pharmacokinetics of Daclizumab High-Yield Process in Healthy Volunteers and Subjects with Multiple Sclerosis: Analysis of Phase I-III Clinical Trials.Clinical pharmacokinetics · 2016Trial
- Population pharmacokinetic and pharmacodynamic analysis of BIIB023, an anti-TNF-like weak inducer of apoptosis (anti-TWEAK) monoclonal antibody.British journal of clinical pharmacology · 2016Trial
- Blockade of the High-Affinity Interleukin-2 Receptors with Daclizumab High-Yield Process: Pharmacokinetic/Pharmacodynamic Analysis of Single- and Multiple-Dose Phase I Trials.Clinical pharmacokinetics · 2016Trial
- Cross-Species Extrapolation of Neonatal Fc Receptor (FcRn) Binding Affinity to Predict Monoclonal Antibody Pharmacokinetics in Humans Using Physiologically Based Pharmacokinetic Modeling (PBPK): Are We There Yet?ACS pharmacology & translational science · 2025Article
- Phase 1 study of isatuximab monotherapy in Chinese patients with relapsed/refractory multiple myeloma.Scientific reports · 2024Article
- Treatment optimization of maintenance immunosuppressive agents in pediatric renal transplant recipients.Expert opinion on drug metabolism & toxicology · 2021Review
- Predicting monoclonal antibody pharmacokinetics following subcutaneous administration via whole-body physiologically-based modeling.Journal of pharmacokinetics and pharmacodynamics · 2020Article
- Understanding Inter-Individual Variability in Monoclonal Antibody Disposition.Antibodies (Basel, Switzerland) · 2019Review
- Review
- Understanding the Monoclonal Antibody Disposition after Subcutaneous Administration using a Minimal Physiologically based Pharmacokinetic Model.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2018Article
- Daclizumab: Development, Clinical Trials, and Practical Aspects of Use in Multiple Sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017Review
- Monoclonal Antibodies for Relapsing Multiple Sclerosis: A Review of Recently Marketed and Late-Stage Agents.CNS drugs · 2017Review
- Review
- Daclizumab.Hospital pharmacy · 2016Article
- Pregnancy Experience: Nonclinical Studies and Pregnancy Outcomes in the Daclizumab Clinical Study Program.Neurology and therapy · 2016Article
- Population PK-PD analyses of CD25 occupancy, CD56British journal of clinical pharmacology · 2016Article
- Article
- Therapeutic efficacy of monthly subcutaneous injection of daclizumab in relapsing multiple sclerosis.Biologics : targets & therapy · 2016Review
- Management of Multiple Sclerosis in the Breastfeeding Mother.Multiple sclerosis international · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveDaclizumab is a humanized monoclonal antibody that blocks the α-subunit of the interleukin-2 receptor with demonstrated benefits in the treatment of multiple sclerosis. The present work aimed to characterize the pharmacokinetics of daclizumab high-yield process (HYP) in healthy volunteers.
methodsThree double-blind, randomized, placebo-controlled, phase I studies evaluated the pharmacokinetics of daclizumab HYP in healthy volunteers following single subcutaneous administration (50, 150, or 300 mg), multiple subcutaneous administrations (100 or 200 mg biweekly with a 200 mg loading dose), or single intravenous administration (200 or 400 mg). Measurable serum concentrations (n = 925) from 70 subjects treated with daclizumab HYP in the three studies were analyzed using non-linear mixed-effects modeling.
resultsA two-compartment model with a first-order absorption and elimination adequately described daclizumab HYP pharmacokinetics. Daclizumab HYP clearance, inter-compartmental clearance, and central and peripheral volumes of distribution were 10 mL/h, 44 mL/h, 3.89 L, and 2.52 L, respectively, scaled by [bodyweight (kg)/70] with 0.54 and 0.64 exponents for clearance and volume parameters, respectively. Lag-time, mean absorption time, and absolute bioavailability (100-300 mg) for subcutaneous administration were 2 h, 4.6 days, and 84 %, respectively. Bodyweight explained only ~20 % of daclizumab HYP pharmacokinetic variability. With this limited dataset, sex, age, race, or presence of antibodies did not correlate with daclizumab HYP clearance. The estimated effective half-life was 21-25 days. The developed model was robust in bootstrap evaluation and predicted the data adequately in stochastic simulations.
conclusionsDaclizumab HYP is characterized by slow clearance, linear pharmacokinetics (at doses ≥100 mg), high subcutaneous bioavailability, and a half-life suitable for monthly administration.
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What OpenQuestion holds
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.