Molnupiravir is an orally administered prodrug of the broadly active, direct-acting antiviral, ribonucleoside analogue ß-d-N4-hydroxycytidine (NHC). It is now emerging as a promising COVID-19 drug candidate.

A study characterised the pharmacokinetics of NHC in saliva, nasal secretions and tears of patients enrolled in phase I AGILE trial to comprehend its potential in preventing infection and transmission.

Patients with PCR-confirmed SARS-CoV-2 infection, within 5 days of symptom onset with the mild-to-moderate disease were enrolled for the study. They were randomised to receive either oral molnupiravir 300, 600 or 800 mg twice daily or a placebo. Plasma and non-plasma (saliva, nasal secretions and tears) samples were collected at pre-dose, 0.5, 1, 2, and 4 hours post-dose on study days 1 and 5 and molnupiravir. NHC was measured by LC/MS with a lower limit of quantification of 2.5 ng/mL in all matrices. Pharmacokinetic parameters were determined and non-plasma: plasma ratios (RNP:P) was calculated.

The following observations were made-

• 12 participants completed the study. 
• NHC Tmax ranged between 1.00-4.00 hours for saliva and nasal swabs and 0.50-4.00 hours for tears compared to 1.00-2.00 hours for plasma. 
• Median saliva RNP:P pooled across doses was found to be 0.03. 
• RNP:P for nasal secretions and tears were 0.21 and 0.22, respectively.  
• A significant correlation between Non-plasma and plasma concentrations was found.

Thus the distribution of NHC at sites of viral transmission is clear from this data, which can be implicated for prophylactic coverage.

Source: medRxiv 2021.12.06.21267342. doi: https://doi.org/10.1101/2021.12.06.21267342