Absorption, Distribution and Excretion
Hydroxychloroquine is 67-74% bioavailable. Bioavailability of the R and S enantiomers were not significantly different. Following a single 200 mg oral dose of hydroxychloroquine to healthy male volunteers, whole blood hydroxychloroquine Cmax was 129.6 ng/mL (plasma Cmax was 50.3 ng/mL) with Tmax of 3.3 hours (plasma Tmax 3.7 hours). Following a single oral hydroxychloroquine dose of 200 mg, the mean fraction of the dose absorbed was 0.74 (compared to the administration of 155 mg of hydroxychloroquine intravenous infusion). Peak blood concentrations of metabolites were observed at the same time as peak levels of hydroxychloroquine. After administration of single 155 mg and 310 mg intravenous doses, peak blood concentrations ranged from 1161 ng/mL to 2436 ng/mL (mean 1918 ng/mL) following the 155 mg infusion and 6 months following the 310 mg infusion. Pharmacokinetic parameters were not significantly different over the therapeutic dose range of 155 mg and 310 mg indicating linear kinetics. In patients with rheumatoid arthritis, there was large variability as to the fraction of the dose absorbed (i.e. 30 to 100%), and mean hydroxychloroquine levels were significantly higher in patients with less disease activity.
40-50% of hydroxychloroquine is excreted renally, while only 16-21% of a dose is excreted in the urine as unchanged drug. 5% of a dose is sloughed off in skin and 24-25% is eliminated through the feces.
Hydroxychloroquine is extensively distributed to tissues; it has a volume of distribution of 5522L from blood and 44,257L from plasma.
The clearance of hydroxychloroquine is 96mL/min. Renal clearance of unchanged drug was approximately 16% to 30%.

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Metabolism / Metabolites
Hydroxychloroquine is N-dealkylated by CYP3A4 to the active metabolite desethylhydroxychloroquine, as well as the inactive metabolites desethylchloroquine and bidesethylchloroquine. Desethylhydroxychloroquine is the major metabolite.
Partially hepatic, to active de-ethylated metabolites.
Half Life: Terminal elimination half-life In blood is approximately 50 days. In plasma it is approximately 32 days.

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Biological Half-Life
A half-life of 123.5 days in plasma was observed following a single 200 mg oral PLAQUENIL dose to healthy male volunteers. Urine hydroxychloroquine levels were still detectable after 3 months with approximately 10% of the dose excreted as the parent drug. Results following a single dose of a 200 mg tablet versus i.v. infusion (155 mg), demonstrated a half-life of about 40 days and a large volume of distribution. Following chronic oral administration of hydroxychloroquine, the absorption half-life was approximately 3 to 4 hours and the terminal half-life ranged from 40 to 50 days.

Toxicity Summary
Although the exact mechanism of action is unknown, it may be based on ability of hydroxychloroquine to bind to and alter DNA. Hydroxychloroquine has also has been found to be taken up into the acidic food vacuoles of the parasite in the erythrocyte. This increases the pH of the acid vesicles, interfering with vesicle functions and possibly inhibiting phospholipid metabolism. In suppressive treatment, hydroxychloroquine inhibits the erythrocytic stage of development of plasmodia. In acute attacks of malaria, it interrupts erythrocytic schizogony of the parasite. Its ability to concentrate in parasitized erythrocytes may account for their selective toxicity against the erythrocytic stages of plasmodial infection. As an antirheumatic, hydroxychloroquine is thought to act as a mild immunosuppressant, inhibiting the production of rheumatoid factor and acute phase reactants. It also accumulates in white blood cells, stabilizing lysosomal membranes and inhibiting the activity of many enzymes, including collagenase and the proteases that cause cartilage breakdown.

Pharmacodynamics
Hydroxychloroquine affects the function of lysosomes in humans as well as plasmodia. Altering the pH of the lysosomes reduces low-affinity self-antigen presentation in autoimmune diseases and interferes with the ability of plasmodia to proteolyze hemoglobin for their energy requirements. Hydroxychloroquine has a long duration of action as it may be taken on a weekly basis for some indications. Hydroxychloroquine may lead to severe hypoglycemia and so diabetic patients are advised to monitor their blood glucose levels. Hydroxychloroquine is active against the erythrocytic forms of chloroquine-sensitive strains of P. falciparum, P. malariae, P. vivax, and P. ovale. Hydroxychloroquine is not active against the gametocytes and exoerythrocytic forms including the hypnozoite liver stage forms of P. vivax and P. ovale. Hydroxychloroquine is not effective against malaria in areas where chloroquine resistance has been reported.

C18H26N3OCL

335.87154

335.176

118-42-3

Hydroxychloroquine sulfate;747-36-4;Hydroxychloroquine-d4-1 sulfate;1216432-56-2;Hydroxychloroquine-d5

3652

White to off-white solid powder

1.176 g/cm3

516.7ºC at 760 mmHg

89-91°

266.3ºC

1.68E-11mmHg at 25°C

1.5790 (estimate)

3.856

48.39

2

4

9

23

331

0

CCN(CCCC(C)NC1=C2C=CC(=CC2=NC=C1)Cl)CCO

XXSMGPRMXLTPCZ-UHFFFAOYSA-N

InChI=1S/C18H26ClN3O/c1-3-22(11-12-23)10-4-5-14(2)21-17-8-9-20-18-13-15(19)6-7-16(17)18/h6-9,13-14,23H,3-5,10-12H2,1-2H3,(H,20,21)

2-[4-[(7-chloroquinolin-4-yl)amino]pentyl-ethylamino]ethanol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~297.73 mM)
1M HCl : 100 mg/mL (~297.73 mM)
H2O : ~1.67 mg/mL (~4.97 mM)

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。