Phase I Pharmacokinetics Study of Drug «COVID-globulin» (Specific Human Immunoglobulin Against COVID-19)
Notice bibliographique
Résumé
Introductio n. Coronavirus infection is an acute viral disease with a predominant lesion of the upper respiratory tract caused by an RNA-containing virus of the Coronaviridae family. However, it is known that neutralizing antibodies play an important role in antiviral therapy because they effectively inhibit the reproduction of viruses and reduce the severity of the disease. Polyclonal antibodies contained in convalescent plasma are usually used as emergency therapy for emerging infectious diseases. In this aspect, the use of a human immunoglobulin G preparation containing specific antibodies to SARS-CoV-2 ("COVID-globulin") appears to be safer and more effective. Aim. The aim is pharmacokinetics study of drug "COVID-globulin" (specific human immunoglobulin against COVID-19, solution for infusions, not less than 160 anti-COVID units/mL (ACU/mL), JSC "NPO Microgen", owner of the registration certificate of JSC "Natsibio", Russia), in addition to standard therapy for the treatment of patients with middle-grade COVID-19. Materials and methods. The clinical and analytical stages of the study of the pharmacokinetics of drug "COVID-globulin", as well as the analysis of the safety and parameters of pharmacokinetics were carried as part of a clinical study of the safety, tolerability and pharmacokinetics of the drug immunoglobulin ("COVID-globulin"), not less than 160 anti-COVID units/mL (ACU/mL), JSC "NPO Microgen", owner of the registration certificate of JSC " Natsibio", Russia. Quantitative determination of antibody concentrations against SARS-CoV-2 was carried out by enzyme-linked immunosorbent assay using spectrophotometric detection in the visible range of the spectrum on an automatic plate enzyme-linked immunosorbent assay analyzer Lazurite (Dynex Technologies Inc., USA). The calculation of pharmacokinetic parameters was carried out using the Microsoft Excel package with an extension for pharmacokinetic analysis Boomer (Department of Pharmacokinetics and Drug Metabolism, Allergan, Irvine, CA 92606, USA). Results and discussion. No serious adverse events were reported in the study, and the only adverse event that resulted in a volunteer withdrawing from the study was not related to the use of the drug. The pharmacokinetic parameters of the drug "COVID-globulin" were calculated for two batches of drugs. The pharmacokinetics of the "COVID-globulin" (the content of antibodies to SARS-CoV-2 – 330 ACU/ml) was assessed on a sample of 8 volunteers. The maximum concentration of specific IgG antibodies to the SARS-CoV-2 virus was 25.46 ± 8.71 ACU/ml (Mean ± SD, where Mean is the arithmetic mean, SD is the standard deviation). The median value of the time to maximum concentration of specific IgG antibodies to the SARS-CoV-2 virus was 0.25 hours. Specific IgG antibodies to the SARS-CoV-2 virus were eliminated from blood plasma with a half-life value 266.89 ± 59.92 hours. The pharmacokinetics of the "COVID-globulin" (the content of antibodies to SARS-CoV-2 – 250 ACU/ml) was assessed on a sample of 15 volunteers. The maximum concentration of specific IgG antibodies to the SARS-CoV-2 virus was 20.93 ± 3.82 ACU/ml. The median value of the time to maximum concentration of specific IgG antibodies to the SARS-CoV-2 virus was 0.25 hours. Specific IgG antibodies to the SARS-CoV-2 virus were eliminated from blood plasma with a half-life value 295.56 ± 50.68 hours. Conclusion. According to the results of the study, the safety profile of the drug "COVID-globulin" is assessed as favorable. Based on the concentrations of specific IgG antibodies to the SARS-CoV-2 virus obtained during the analytical stage of the study, the main pharmacokinetic parameters were calculated, and the average pharmacokinetic profiles of the test drug "COVID-globulin" were plotted after a single injection. The results obtained were the basis for the subsequent phases of clinical trials of the drug "COVID-globulin".
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».