Pharmacokinetics of ß-d-N4-Hydroxycytidine, the Parent Nucleoside of Prodrug Molnupiravir, in Nonplasma Compartments of Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection
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Abstract
ß-d-N4-hydroxycytidine (NHC), the parent nucleoside of molnupiravir, a COVID-19 antiviral, was quantified at SARS-CoV-2 transmission sites in 12 patients enrolled in AGILE Candidate-Specific Trial-2. Saliva, nasal, and tear NHC concentrations were 3%, 21%, and 22% that of plasma. Saliva and nasal NHC were significantly correlated with plasma (P < .0001).
Clinical Trials Registration. NCT04746183.
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SciScore for 10.1101/2021.12.06.21267342: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study was approved by the UK Medicines and Healthcare product Regulatory Agency (MHRA; EudraCT 2020– 001860-27) and West Midlands Edgbaston Research Ethics Committee (20/ WM/0136) and all individuals provided written informed consent.
Consent: The study was approved by the UK Medicines and Healthcare product Regulatory Agency (MHRA; EudraCT 2020– 001860-27) and West Midlands Edgbaston Research Ethics Committee (20/ WM/0136) and all individuals provided written informed consent.
Field Sample Permit: All pharmacokinetic specimens were transported and processed on wet ice and stored at -80°C within 60 minutes of collection.Sex as a biological variable not detected. Randomization In brief, … SciScore for 10.1101/2021.12.06.21267342: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study was approved by the UK Medicines and Healthcare product Regulatory Agency (MHRA; EudraCT 2020– 001860-27) and West Midlands Edgbaston Research Ethics Committee (20/ WM/0136) and all individuals provided written informed consent.
Consent: The study was approved by the UK Medicines and Healthcare product Regulatory Agency (MHRA; EudraCT 2020– 001860-27) and West Midlands Edgbaston Research Ethics Committee (20/ WM/0136) and all individuals provided written informed consent.
Field Sample Permit: All pharmacokinetic specimens were transported and processed on wet ice and stored at -80°C within 60 minutes of collection.Sex as a biological variable not detected. Randomization In brief, eligible individuals were randomly assigned to one of three sequential dosing cohorts - molnupiravir dosed orally at 300, 600 and 800 mg twice daily. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Data were log transformed and analysed using IBM SPSS Statistics (v. 25.0 SPSSsuggested: (SPSS, RRID:SCR_002865)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:There are a number of limitations. We utilised a sampling schedule for a truncated pharmacokinetic profile (0-4 hours) to limit infection risk. Missing samples led to a number of exclusions from the analysis, particularly for evaluation of RNP:P, contributed to data variability and limited data interpretation. Finally, the active triphosphate metabolite, EIDD-2061 was not quantified. Despite the limitations these data add to our understanding of NHC pharmacokinetics, principally at sites of COVID-19 infection. To our knowledge this is the first report describing significant accumulation of NHC in nasal secretions and tears, and to a lesser extent saliva. These data support the evaluation of molnupiravir as prophylaxis for SARS-CoV-2 infection.
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04746183 Recruiting AGILE (Early Phase Platform Trial for COVID-19) NCT04939428 Recruiting Study of MK-4482 for Prevention of Coronavirus Disease 2019 … Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a protocol registration statement.
Results from scite Reference Check: We found no unreliable references.
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