A review on the pharmacokinetic properties and toxicity considerations for chloroquine and hydroxychloroquine to potentially treat coronavirus patients

Abstract

The SARS-CoV-2 virus, caused a novel emerged coronavirus disease, is growing rapidly worldwide. Few studies have evaluated the efficacy and safety of Chloroquine (CQ), an old antimalarial drug, and Hydroxychloroquine (HCQ) in the treatment of COVID-19 infection. HCQ is derived from CQ by adding a hydroxyl group into it and is a less toxic derivative of CQ for the treatment of COVID-19 infection because it is more soluble. This article summarizes pharmacokinetic properties and toxicity considerations for CQ and HCQ, drug interactions, and their potential efficacy against COVID-19. The authors also look at the biochemistry changes and clinical uses of CQ and HCQ, and supportive treatments following toxicity occurs. It was believed that CQ and HCQ may provide few benefits to COVID-19 patients. A number of factors should be considered to keep the drug safe, such as dose, in vivo animal toxicological findings, and gathering of metabolites in plasma and/or tissues. The main conclusion of this review is that CQ and HCQ with considered to their ADMET properties has major shortcomings and fully irresponsible.

CHIKV strains Brazil (wt) and Ross (lab-adapted) differ with regard to cell host range and antiviral sensitivity and show CPE in human glioblastoma cell lines U138 and U251

“…Differences in the E1 protein between the two strains may be responsible for the differences in HCQ response, as HCQ (and the more toxic base substance chloroquine (CQ)) is known to raise the endosomal pH and thus intervene with CHIKV membrane fusion [ 57 ]. It is therefore possible that some of these changes have an impact on the acid pH-triggered conformational changes in alphavirus E1 during membrane fusion [ 58 ].…”

The marine natural product, dicitrinone B, induces apoptosis through autophagy blockade in breast cancer

“…The autophagy inhibitors, cQ and hydroxychloroquine (HCQ), have shown promising efficacy in breast cancer and triple-negative breast cancer pre-clinical models or in clinical trials when combined with other conventional chemotherapies (42,43). However, the retinal toxicity of cQ/HcQ has also attracted increased attention (44)(45)(46)(47). Therefore, the research and development of novel autophagy inhibitors is of utmost clinical significance in cancer treatment.…”