Pharmacology of Chloroquine and Hydroxychloroquine
Review of the pharmacology of CQ and HCQ. Some notable points:
- HCQ and CQ are equipotent but CQ is more toxic, the therapeutic ratio is higher for HCQ.
- Concentrations in different tissues can vary >10x, in particular the concentration in the lung is much higher in animal experiments.
- Tissue uptake as a function of dosage is nonlinear.
26 preclinical studies support the efficacy of HCQ for COVID-19:
18 In Vitro studies Alsmadi, Andreani, Clementi, Dang, Delandre, Faísca, Kamga Kapchoup, Liu, Milan Bonotto, Ou, Purwati, Shang, Sheaff, Wang, Wang (B), Wen, Yao, Yuan
Browning et al., 4 Apr 2014, peer-reviewed, 1 author.
Abstract: 2
Pharmacology of Chloroquine
and Hydroxychloroquine
Abbreviations
4AQR
4AQs
ABW
APC
BCVA
C
CpG ODN
CV
CYP
DFE
DNA
ERK
FP
GVF
HC
HIV
HMG-CoA
IBW
IFN
IL
LD50
LDL
M
mRNA
NG
RA
RNA
RPE
4-Aminoquinoline retinopathy
4-Aminoquinolines (chloroquine
and hydroxychloroquine)
Actual body weight
Antigen presenting cell
Best corrected visual acuity
Chloroquine
CpG oligodeoxynucleotide
Color vision
Cytochrome P450 enzymes
Dilated fundus examination
Deoxyribonucleic acid
Extracellular
signal-regulated
kinases
Ferriprotoporphyrin IX
Goldmann visual fields
Hydroxychloroquine
Human immunodeficiency virus
3-Hydroxy-3-methylglutarylcoenzyme A reductase
Ideal body weight
Interferon
Interleukin
Lethal dose 50
Low-density lipoprotein
Mole
Mitochondrial ribonucleic acid
Not given
Rheumatoid arthritis
Ribonucleic acid
Retinal pigment epithelium
SARS
SLE
TLR
TNF
TNF-α
V
Severe acute respiratory syndrome
Systemic lupus erythematosus
Toll-like receptor
Tumor necrosis factor
Tumor necrosis factor α
Volume of distribution
This chapter covers the pharmacology of chloroquine and hydroxychloroquine, which is similar for
both drugs [1], but the details are different. For
example, both drugs are partially excreted in feces,
but the proportions differ slightly—8–10 % for
chloroquine and 15–24 % for hydroxychloroquine.
Generally, whatever is said in this chapter about one
drug can be assumed to apply to the other unless
otherwise specified [1, 2]. Because both drugs are
derivatives of a 4-aminoquinoline (4AQ) nucleus,
they are referred to as 4AQs, and the retinopathy
that they can cause is termed 4-aminoquinoline retinopathy (4AQR) [3]. Commonly used abbreviations in this chapter are collected in “Abbreviations”
for reference. Each term will be first used in its full
form, along with its abbreviation.
2.1
History
In the 1600s, the Jesuits who proselytized Chile
discovered from the Incas that the bark of the cinchona tree can cure malaria [4, 5]. Additional
medicinal qualities of cinchona bark were described
in the 1700s, and the British and Dutch transplanted
these trees to Javan plantations in the early 1900s
D.J. Browning, Hydroxychloroquine and Chloroquine Retinopathy,
DOI 10.1007/978-1-4939-0597-3_2, © Springer Science+Business Media New York 2014
35
2
Pharmacology of Chloroquine and Hydroxychloroquine
for the production of quinine. In 1894, Payne
described the use of quinine to treat systemic lupus
erythematosus (SLE) [6]. Other alkaloids contained in cinchona bark, such as pamaquine, were
also successfully used to treat SLE [5].
When the Japanese army occupied Java in
World War II, the natural supply of quinine was
lost, and synthesis of antimalarials was pursued
in the United States [7]. Quinacrine, a
9-aminoacridine compound, was first used, but
had the unpleasant side effect of staining the skin
and sclera yellow in a manner indistinguishable
from icterus [8–10]. The 4AQs, chloroquine and
hydroxychloroquine, were found to be effective
as antimalarials and did not discolor the skin.
Chloroquine was first synthesized in 1934 by
Andersag of I.G. Farbenindustrie in a German
effort to find drugs better than quinine [11]. The
Germans lost interest in the drug when they
judged it to be too toxic for use in man, but the
Americans restudied the drug and found it to be
effective against malaria and sufficiently safe [3,
7, 12]. Hydroxychloroquine was synthesized in
1946 and proposed as a safer alternative to chloroquine in 1955 [13]. Resistance to..
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