Pharmacology of Chloroquine and Hydroxychloroquine

Browning, David J.

doi:10.1007/978-1-4939-0597-3_2

Cited by 153 publications

(171 citation statements)

References 199 publications

Supporting

Mentioning

152

Contrasting

Unclassified

Order By: Relevance

“…31,33,42 Fourthly, the steady state CQ/HCQ concentrations of 1 μg/mL (~3.125 μM/L) and~16 μM/L detected in plasma and whole blood respectively, have been shown both in vivo and in vitro to inhibit viral replication and the overproduction of some immunological mediators associated with the pathologies of many viral infections and some autoimmune diseases. 22,48,64,[68][69][70] I conclude that (1) a 16 μM/L transient or steady state whole blood concentration of CQ most likely has no significant cardiovascular events 22,42,67-69 ; (2)~16 μM/L steady state whole blood concentration of CQ/HCQ is able to inhibit viral replication, glycosylation and the over production of some immunological mediators associated with some viral infections 22,33-35,38,39,42,64,67-70 ; (3) the optimal uptake of CQ in humans is likely to lie within the range of 10-20 μM/L. Therefore, such a steady state CQ concentration could be safe and sufficient to raise and maintain the acidic organelles' pH to a level approximately neutral, thereby inhibiting viral replication by mechanisms such as inhibition of endosomal proteases, inhibition of the fusion of viral membrane with host cells plasma membranes and inhibition of viral glycosylation.…”

Section: Sufficient Steady State Chloroquine Concentrations May Be Nementioning

confidence: 99%

Chloroquine could be used for the treatment of filoviral infections and other viral infections that emerge or emerged from viruses requiring an acidic pH for infectivity

Akpovwa

2016

Cell Biochemistry & Function

View full text Add to dashboard Cite

Viruses from the Filoviridae family, as many other virus families, require an acidic pH for successful infection and are therefore susceptible to the actions of 4‐aminoquinolines, such as chloroquine.Although the mechanisms of action of chloroquine clearly indicate that it might inhibit filoviral infections, several clinical trials that attempted to use chloroquine in the treatment of other acute viral infections – including dengue and influenza A and B – caused by low pH‐dependent viruses, have reported that chloroquine had no clinical efficacy, and these results demoted chloroquine from the potential treatments for other virus families requiring low pH for infectivity.The present review is aimed at investigating whether chloroquine could combat the present Ebola virus epidemic, and also at exploring the main reasons for the reported lack of efficacy. Literature was sourced from PubMed, Scopus, Google Scholar, reference list of articles and textbooks – Fields Virology (Volumes 1and 2), the cytokine handbook, Pharmacology in Medicine: Principles and Practice, and hydroxychloroquine and chloroquine retinopathy.The present analysis concludes that (1) chloroquine might find a place in the treatment of Ebola, either as a monotherapy or in combination therapies; (2) the ineffectiveness of chloroquine, or its analogue, hydroxychloroquine, at treating infections from low pH‐dependent viruses is a result of the failure to attain and sustain a steady state concentration sufficient to increase and keep the pH of the acidic organelles to approximately neutral levels; (3) to successfully treat filoviral infections – or other viral infections that emerge or emerged from low pH‐dependent viruses – a steady state chloroquine plasma concentration of at least 1 µg/mL(~3.125 μM/L) or a whole blood concentration of 16 μM/L must be achieved and be sustained until the patients' viraemia becomes undetectable. These concentrations, however, do not rule out the efficacy of other, higher, steady state concentrations – although such concentrations might be accompanied by severe adverse effects or toxicities. The feasibility of the conclusion in the preceding texts has recently been supported by a subsequent study that shows that amodiaquine, a derivative of CQ, is able to protect humans infected with Ebola from death.

show abstract

Section: Sufficient Steady State Chloroquine Concentrations May Be Nementioning

confidence: 99%

Chloroquine could be used for the treatment of filoviral infections and other viral infections that emerge or emerged from viruses requiring an acidic pH for infectivity

Akpovwa

2016

Cell Biochemistry & Function

View full text Add to dashboard Cite

show abstract

“…Chloroquine, a 4-aminoquinoline, is a weak base that is rapidly imported into acidic vesicles, increasing their pH [18]. It is approved by the Food and Drug Administration (FDA) to treat malaria and has long been prophylactically prescribed to pregnant women at risk of exposure to Plasmodium parasites [19].…”

Section: Introductionmentioning

confidence: 99%

Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models

Delvecchio

Higa

Pezzuto

et al. 2016

Viruses

239

201

View full text Add to dashboard Cite

Zika virus (ZIKV) infection in utero might lead to microcephaly and other congenital defects. Since no specific therapy is available thus far, there is an urgent need for the discovery of agents capable of inhibiting its viral replication and deleterious effects. Chloroquine is widely used as an antimalarial drug, anti-inflammatory agent, and it also shows antiviral activity against several viruses. Here we show that chloroquine exhibits antiviral activity against ZIKV in Vero cells, human brain microvascular endothelial cells, human neural stem cells, and mouse neurospheres. We demonstrate that chloroquine reduces the number of ZIKV-infected cells in vitro, and inhibits virus production and cell death promoted by ZIKV infection without cytotoxic effects. In addition, chloroquine treatment partially reveres morphological changes induced by ZIKV infection in mouse neurospheres.

show abstract

“…They are found to inhibit CD4 T-cell stimulation while also promoting CD8 T-cell stimulation, and hence they are a popular choice for controlling the progression of autoimmune diseases without increasing the rate of opportunistic infections 1. HCQ is more molecularly polar than CQ making it less lipophilic, leading to poorer diffusion through biological membranes and resulting in less toxicity 1. One of the most severe complications of these drugs is retinopathy, which leads to visual field defects and visual loss as a result of damaged photoreceptors.…”

Section: Introductionmentioning

confidence: 99%

Incidence of and risk factors for chloroquine and hydroxychloroquine retinopathy in Thai rheumatologic patients

Tangtavorn

Yospaiboon

Ratanapakorn

et al. 2016

OPTH

View full text Add to dashboard Cite

ObjectiveTo study the incidences of and risk factors for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy in Thai rheumatologic patients.MethodsA retrospective cohort study of 234 rheumatologic patients receiving either CQ or HCQ was conducted. Patients were divided based on whether or not they developed retinopathy as retinopathy-positive or negative groups. Medical records giving details regarding age, gender, body weight, underlying diseases, daily doses, and cumulative doses of CQ or HCQ were reviewed. CQ and HCQ retinopathy were diagnosed by indirect ophthalmoscopy, Humphrey visual field test, and optical coherence tomography. The main outcome measures were incidences and risk factors of CQ and HCQ retinopathy.ResultsThe CQ retinopathy was detected in 14 of 173 patients (8.09%) who received CQ for 139–2,033 days, cumulative doses from 14.3 to 325.1 g, and daily doses from 0.8 to 18.5 mg/kg/d. Their ages ranged from 27 to 65 years. When compared to the CQ retinopathy-negative group, only age, body weight, and cumulative dose showed statistically significant differences. The HCQ retinopathy-positive group was comprised of 2 of 61 patients (3.28%) who received HCQ for 660–828 days, cumulative doses from 80 to 130 g, and daily dose from 1.9 to 4.4 mg/kg/d. Their ages were 36 and 39 years. Compared to the HCQ retinopathy-negative group, there were no statistically significant differences in studied risk factors.ConclusionIncidences of and risk factors for CQ and HCQ retinopathy were reported. Since most patients developed retinopathy earlier than 5 years, it is suggested that patients taking long-term CQ or HCQ should undergo ophthalmologic screening annually after the baseline examination.

show abstract

Pharmacology of Chloroquine and Hydroxychloroquine

Cited by 153 publications

References 199 publications

Chloroquine could be used for the treatment of filoviral infections and other viral infections that emerge or emerged from viruses requiring an acidic pH for infectivity

Chloroquine could be used for the treatment of filoviral infections and other viral infections that emerge or emerged from viruses requiring an acidic pH for infectivity

Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models

Incidence of and risk factors for chloroquine and hydroxychloroquine retinopathy in Thai rheumatologic patients

Contact Info

Product

Resources

About