Translate this page into:
Authors’ response
*For correspondence: director@nariindia.org
This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
This article was originally published by Wolters Kluwer - Medknow and was migrated to Scientific Scholar after the change of Publisher.
We thank the author for a close reading of our article and for suggesting an alternate dosing regimen of HCQ for prophylaxis against SARS-CoV-2 infection1. Given that the dosing proposed by the author is higher than the current recommendation, we feel that it would be prudent to establish the safety as well as efficacy of the proposed regimen through clinical studies. There is evidence from physiology-based pharmacokinetic models, which suggest that even at lower doses HCQ can attain pulmonary concentrations at which it may exhibit anti-SARS-CoV-2 properties in vitro2. Other models, which define the distribution of CQ in human beings, have suggested that once weekly dosing regimen could help attain effective drug concentration in the lungs3.
Further, single-dose kinetic studies of CQ used for malaria chemoprophylaxis indicate that adequate plasma concentrations are achieved after four weeks of use, before which the individual remains susceptible to contract malaria4. We further agree with the author that it is likely to take some time before the dose-dependent effect of HCQ countering SARS-CoV-2 infection starts operating in vivo56 through effective concentration built-up in the lungs.
We conclude that the currently recommended regimen has some supporting evidence based on laboratory studies and clinical experience of using HCQ for malaria chemoprophylaxis. We also maintain that it would be more appropriate to adhere to stringent use of PPE and preventive measures, such as personal hygiene, social distancing and frequent hand washing along with the currently recommended regimen of HCQ prophylaxis for healthcare workers, until the safety of a higher dose regimen is demonstrated in clinical studies.
References
- Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19. Indian J Med Res. 2020;151:459-67.
- [Google Scholar]
- In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Clin Infect Dis. 2020;71:732-9.
- [Google Scholar]
- Modelling of systemic versus pulmonary chloroquine exposure in man for COVID-19 dose selection medRxiv. 2020 doi: 101101/2020042420078741
- [Google Scholar]
- The single dose kinetics of chloroquine and its major metabolite desethylchloroquine in healthy subjects. Eur J Clin Pharmacol. 1984;26:521-30.
- [Google Scholar]
- Kinetics of the distribution and elimination of chloroquine in the rat. Gen Pharmacol. 1982;13:433-7.
- [Google Scholar]
- Chloroquine for SARS-CoV-2: Implications of its unique pharmacokinetic and safety properties. Clin Pharmacokinet. 2020;59:659-69.
- [Google Scholar]