Trial reportClinical pharmacokinetics2019
Population Pharmacokinetic Analysis of Alirocumab in Healthy Volunteers or Hypercholesterolemic Subjects Using a Michaelis-Menten Approximation of a Target-Mediated Drug Disposition Model-Support for a Biologics License Application Submission: Part I.
Trial report in Clinical pharmacokinetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic Review of Device Parameters and Design of Studies Bridging Biologic-Device Combination Products Using Prefilled Syringes and Autoinjectors.The AAPS journal · 2020Pooled it
- Population Pharmacokinetic/Pharmacodynamic Modeling of Volagidemab, a Glucagon Receptor Antagonist, in Healthy Chinese and US Subjects Following Single Subcutaneous Administration.Pharmaceutical research · 2026Trial
- Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Alirocumab in Healthy Chinese Subjects: A Randomized, Double-Blind, Placebo-Controlled, Ascending Single-Dose Study.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2020Trial
- Population Pharmacokinetic/Pharmacodynamic Analysis of Alirocumab in Healthy Volunteers or Hypercholesterolemic Subjects Using an Indirect Response Model to Predict Low-Density Lipoprotein Cholesterol Lowering: Support for a Biologics License Application Submission: Part II.Clinical pharmacokinetics · 2019Trial
- PK and PK/PD Modeling of Bcl2 Inhibitor S65487 in Patients With AML and Investigation of Nonlinearity With Microdosing.CPT: pharmacometrics & systems pharmacology · 2026Article
- Article
- Pharmacological considerations for next-generation protein therapeutics in cardiovascular disease.The Journal of pharmacology and experimental therapeutics · 2025Review
- Target-Mediated Modeling of Alirocumab in Adolescents and Children ≥8 to <12 Years of Age Using Phase II and III Data.Clinical pharmacology in drug development · 2025Article
- Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets.Chinese journal of integrative medicine · 2024Review
- Model-Informed Dose Selection for a Novel Human Immunoglobulin G4 Derived Monoclonal Antibody Targeting Proprotein Convertase Kwashiorkor Type 9: Insights from Population Pharmacokinetics-Pharmacodynamics and Systems Pharmacology.ACS pharmacology & translational science · 2024Article
- Pharmacokinetic/LDL-C and exposure-response analysis of tafolecimab in Chinese hypercholesterolemia patients: Results from phase I, II, and III studies.Clinical and translational science · 2023Article
- Adults on pre-exposure prophylaxis (tenofovir-emtricitabine) have faster clearance of anti-HIV monoclonal antibody VRC01.Nature communications · 2023Article
- Proprotein Convertase Subtilisin/Kexin 9 as a Modifier of Lipid Metabolism in Atherosclerosis.Biomedicines · 2023Review
- Population Pharmacokinetics of Patritumab Deruxtecan in Patients With Solid Tumors.Journal of clinical pharmacology · 2023Article
- Combined Semi-mechanistic Target-Mediated Drug Disposition and Pharmacokinetic-Pharmacodynamic Models of Alirocumab, PCSK9, and Low-Density Lipoprotein Cholesterol in a Pooled Analysis of Randomized Phase I/II/III Studies.European journal of drug metabolism and pharmacokinetics · 2022Article
- Musculoskeletal Adverse Events Associated with PCSK9 Inhibitors: Disproportionality Analysis of the FDA Adverse Event Reporting System.Cardiovascular therapeutics · 2022Article
- Population pharmacokinetics and exposure-response modeling for evinacumab in homozygous familial hypercholesterolemia.CPT: pharmacometrics & systems pharmacology · 2021Article
- Development of a Pharmacokinetic Model Describing Neonatal Fc Receptor-Mediated Recycling of HL2351, a Novel Hybrid Fc-Fused Interleukin-1 Receptor Antagonist, to Optimize Dosage Regimen.CPT: pharmacometrics & systems pharmacology · 2020Article
- Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Dupilumab in Healthy Adult Subjects.Clinical pharmacology in drug development · 2020Article
- Pharmacokinetic Variability of Therapeutic Antibodies in Humans: A Comprehensive Review of Population Pharmacokinetic Modeling Publications.Clinical pharmacokinetics · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlirocumab, a human monoclonal antibody, inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) to significantly reduce low-density lipoprotein cholesterol levels; pharmacokinetics (PK) are governed by non-linear, target-mediated drug disposition (TMDD).
objectivesWe aimed to develop and qualify a population PK (PopPK) model to characterize the PK profile of alirocumab, evaluate the impact of covariates on alirocumab PK and on individual patient exposures, and estimate individual predicted concentrations for a subsequent PK/pharmacodynamic (PD) analysis.
methodsData from 13 phase I-III trials of 2799 healthy volunteers or patients with hypercholesterolemia treated with intravenous or subcutaneous alirocumab (13,717 alirocumab concentrations) were included; a Michaelis-Menten approximation of the TMDD model was used to estimate PK parameters and exposures. The final model comprised two compartments with first-order absorption. Elimination from the central compartment was described by linear (CLL) and non-linear Michaelis-Menten clearance (Vm and Km). The model was validated using visual predictive check and bootstrap methods. Patient exposures to alirocumab were computed using individual PK parameters.
resultsThe PopPK model was well-qualified, with the majority of observed alirocumab concentrations in the 2.5th-97.5th predicted percentiles. Covariates responsible for interindividual variability were identified. Body weight and concomitant statin administration impacted CLL, whereas time-varying free PCSK9 concentrations and age affected Km and peripheral distribution volume (V3), respectively. No covariates were clinically meaningful, therefore no dose adjustments were needed.
conclusionsThe model explained the between-subject variability, quantified the impact of covariates, and, finally, predicted alirocumab concentrations (subsequently used in a PopPK/PD model, see Part II) and individual exposures.
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