A POSSIBLE ROLE FOR SINGLE DOSE HYDROXYCHLOROQUINE FOR PREVENTION OF LETHAL CORONAVIRUS INFECTION
A POSSİBLE ROLE FOR SINGLE DOSE HYDROXYCHLOROQUINE FOR PREVENTİON OF LETHAL CORONAVIRUS INFECTİON
Süalp Tansan, M.D.
Coronavirus Disease (COVID-19) is a new strain of coronavirus family of viruses that was discovered in 2019. Common signs of infection include respiratory symptoms, fever, cough, shortness of breath and breathing difficulties. In more severe cases, infection can cause pneumonia, severe acute respiratory syndrome, kidney failure and even death.
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) first broke out in Wuhan, China and later spread worldwide. As of March 21, there are more than 250000 confirmed cases and moer than 14000 deaths reported. Currently, there are no medications or vaccines that have been proven to be effective to prevent COVID-19.
Chloroquine has been used in treating SARS-Cov-2 infection. It is a widely used anti-malarial with immunomodulatory effects (1). It was found to inhibit the growth of SARS-CoV-2 in vitro (2) and in clinical studıes (3).
Hydroxychloroquine is an analog of chloroquine that is widely used in treatment of common medical conditions particularly in rheumatological diseases and as treatment and prophylaxis in Malaria. It has previously been shown to be much less toxic than chloroquine in animals (4). Recently, hydroxychloroquine was shown to be effective in inhibiting SARS-CoV-2 infection in vitro (5). With accumulating clinical evidence, hydroxychloroquine appears to be a clinically efective agent for the treatment of SARS-CoV-2 infection in combination with azitromycin (6).
Hydroxychloroquine is currenly used for prohylaxis of Malaria. The recommended dose is 400 mg weekly (CDC). This dose is sufficient to prevent malaria in the bloodstream.
It is noteworthy that the incidence and mortality of COVID-19 is much less in countries with malaria prevention than countries where no malaria prevention is recommended (7)
At EC50 values of 6.25 micromolar at 24 hours after a single dose of 800 mg, hydroxycholoroquine may be a promising drug for prevention of SARS-CoV-19 (8). Hydroxychloroquine metabolites can accumulate at highest concentration in liver, adrenal and lung tissue in rodents (9). Physiologically-based pharmacokinetic models (PBPK) implemented by integrating in vitro data and simulating the concentration of hydroxychloroquine in lung fluid suggests that a single dose of hydroxychloroquine at 800 mg. may provide a lung tissue concentration that is more than twenty times higher than EC50 values necessary to inhibit SARS-CoV-2 in the lung on day 1 (8). It is plausable that a single dose of 400 mg or even 200 mg can provide adequate lung tissue concentration to inhibit SAR-CoV-2. Since the half life after a single dose of 200 mg is 22 days (FDA data), a single dose every week or even every three weeks should be sufficient for prevention of SARS-CoV-2 induced lung damage. At these doses and schedules. Hydroxychloroquine should be well tolerated and unlikely to cause significant druğ-drug interactions.
The blood or sinus concentrations may not be sufficient to eradicate the virus, however prevention of lung damage may convert this deadly infection into an upper respiratory infection.
In an era where it may take 12-18 months for the wide application of an effective vaccine, and while waiting for the results of properly conducted clinical studies for prevention of COVID-19, hydroxychloroquine may be a practical, cheap, safe and effective agent for prevention of potentailly lethal SARS-C0V-2 infection.
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