Pharmacist's perspective on HCQ treatment of COVID-19.

Abstract

So far, many studies on Hydroxychloroquine (HCQ) treatment of COVID-19 have been published. Since HCQ is widely used for the treatment of Systemic Lupus Erythematosus (SLE) and Rheumatoid arthritis (RA), we will use the pharmacodynamic/pharmacokinetic (PD/PK) data of HCQ to discuss the role of HCQ in COVID-19 treatment. After oral absorption, HCQ is widely distributed in various tissues in the body. According to the results of animal experiments, the tissues with the most HCQ distribution were the lungs, with a concentration of up to 227 times that of plasma, followed by the spleen, liver, and kidney.1 This finding is similar to another in-vitro study on the physiologically based pharmacokinetic (PBPK) model, which was carried out with cells infected by SARS-CoV-2. On the 5th day after continuous use, HCQ concentration in the lung tissue can be more than 85.4 times of EC50.2 In addition, due to the high proportion of HCQ distributed in tissues, the elimination half-life is relatively long. The average half-life of HCQ in a single dose of 400 mg is 172 h, and that of long-term users is 40-50 days. Based on the above PK characteristics of HCQ, we reviewed the literatures on COVID-19 treatment with HCQ and some issues worthy of discussion. First, the clinical trial conducted by Gautret et al. took the virus clearance rate on the 6th day of treatment as the primary endpoint of the study.3 However, there was no credible evidence for the correlation between the virus clearance rate of nasopharynx swab on the 6th day and the subsequent effect maintenance, clinical effectiveness, systemic virus quantity, and whether the virus test would turn positive after drug withdrawal. Second, the concentrations of HCQ distributed in various tissues are much higher than that in blood, especially in the lung tissues. However, it is still unknown whether the concentration in the lung tissues has a positive correlation with the ability to clear the virus from the lung tissue or whether it is correlated with the clinical therapeutic effect and the remission of symptoms. Third, the clinical manifestations of COVID-19 patients include not only respiratory symptoms, but also gastrointestinal or neurological manifestations, and it is also unknown whether the distribution of HCQ in tissues can solve the related symptoms. Not surprisingly, the studies of Molina and Geleris both showed the negative results of HCQ.4, 5 Although HCQ is safer and more effective than Chloroquine, special attention should be paid to the interaction and side effects when it is used with Azithromycin. Especially in terms of cardiovascular, both HCQ and Azithromycin are likely to cause arrhythmias (such as QT prolongation and torsades de points), and combined use will increase the incidence, which was also observed by Molina.4 There's no guidance for the treatment of COVID-19 has indicated that the dose of HCQ can be calculated according to body weight and adjusted according to different races. Further studies are needed in the future to provide more comprehensive data. All authors declare no conflict of interest.