Trial reportClinical pharmacokinetics2022
Pharmacokinetic/Pharmacodynamic Modelling of Allopurinol, its Active Metabolite Oxypurinol, and Biomarkers Hypoxanthine, Xanthine and Uric Acid in Hypoxic-Ischemic Encephalopathy Neonates.
Trial report in Clinical pharmacokinetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03162653 (Effect of ALlopurinol in Addition to Hypothermia for Hypoxic-ischemic Brain Injury on Neurocognitive Outcome - a Blinded Randomized Placebo-controlled Parallel Group Multicenter Trial for Superiority), which is not on this map. Cited by 11 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.
Effect of ALlopurinol in Addition to Hypothermia for Hypoxic-ischemic Brain Injury on Neurocognitive Outcome - a Blinded Randomized Placebo-controlled Parallel Group Multicenter Trial for Superiority (Phase III)
Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Population Pharmacokinetics and Target Attainment of Allopurinol and Oxypurinol Before, During, and After Cardiac Surgery with Cardiopulmonary Bypass in Neonates with Critical Congenital Heart Disease.Clinical pharmacokinetics · 2024Trial
- Time-dependent pattern of liver injury biomarkers in neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia.European journal of pediatrics · 2026Article
- Pharmacological Therapies for Consequences of Perinatal Hypoxic-Ischemic Brain Injury: Where Are We Now?International journal of molecular sciences · 2025Review
- Review
- Antioxidant Therapy in Neonatal Hypoxic Ischemic Encephalopathy: Adjuvant or Future Alternative to Therapeutic Hypothermia?Metabolites · 2024Review
- Neonatal encephalopathy due to suspected hypoxic ischemic encephalopathy: pathophysiology, current, and emerging treatments.World journal of pediatrics : WJP · 2024Review
- A narrative review on treatment strategies for neonatal hypoxic ischemic encephalopathy.Translational pediatrics · 2023Review
- Semi-mechanistic Modeling of Hypoxanthine, Xanthine, and Uric Acid Metabolism in Asphyxiated Neonates.Clinical pharmacokinetics · 2022Article
- Treatments and therapeutic protocols for the recovery of an asphyxiated new-born: A review of pre-clinical and clinical studies in human neonates and in different animal models.Veterinarni medicina · 2022Review
- New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy.European journal of pediatrics · 2022Review
- Correlation of uric acid with microalbuminuria in Type-2 diabetic patients with normal creatinine.Pakistan journal of medical sciencesArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundAllopurinol, an xanthine oxidase (XO) inhibitor, is a promising intervention that may provide neuroprotection for neonates with hypoxic-ischemic encephalopathy (HIE). Currently, a double-blind, placebo-controlled study (ALBINO, NCT03162653) is investigating the neuroprotective effect of allopurinol in HIE neonates.
objectiveThe aim of the current study was to establish the pharmacokinetics (PK) of allopurinol and oxypurinol, and the pharmacodynamics (PD) of both compounds on hypoxanthine, xanthine, and uric acid in HIE neonates. The dosage used and the effect of allopurinol in this population, either or not undergoing therapeutic hypothermia (TH), were evaluated.
methodsForty-six neonates from the ALBINO study and two historical clinical studies were included. All doses were administered on the first day of life. In the ALBINO study (n = 20), neonates received a first dose of allopurinol 20 mg/kg, and, in the case of TH (n = 13), a second dose of allopurinol 10 mg/kg. In the historical cohorts (n = 26), neonates (all without TH) received two doses of allopurinol 20 mg/kg in total. Allopurinol and oxypurinol population PK, and their effects on inhibiting conversions of hypoxanthine and xanthine to uric acid, were assessed using nonlinear mixed-effects modelling.
resultsAllopurinol and oxypurinol PK were described by two sequential one-compartment models with an autoinhibition effect on allopurinol metabolism by oxypurinol. For allopurinol, clearance (CL) was 0.83 L/h (95% confidence interval [CI] 0.62-1.09) and volume of distribution (V
conclusionThe PK and PD of allopurinol, oxypurinol, hypoxanthine, xanthine, and uric acid in neonates with HIE were described. The dosing regimen applied in the ALBINO trial leads to the targeted XO inhibition in neonates treated with or without TH.
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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 Socratic graph.