TMC125 对 HIV-2 (EC50=3.5 μM) 和野生型 HIV-1 (50% 有效浓度 [EC50]=1.4 至 4.8 nM) 表现出显着功效。许多 HIV-1 M 亚型、循环重组形式和 O 组病毒也被 TMC125 抑制。 19 种病毒具有 TMC125 活性，EC50 小于 5 nM[1]。

依曲韦林耐药性的产生具有很强的遗传耐药性。在涉及有治疗经验的个体（包括那些感染了对 NNRTI 和蛋白酶抑制剂 (PI) 耐药的病毒的患者）的 IIb 期试验中，TMC125 已证明具有对抗 HIV 对当前可用 NNRTI 耐药性的活性，同时保持与对照组相当的耐受性[2]。

Absorption, Distribution and Excretion
Maximum oral absorption is achieved in 2.5-4 hours. Absorption is unaffected by the concomitant use of oral ranitidine or omeprazole, which decrease gastric acidity. Administration under fasting conditions resulted in a near 50% decrease in systemic exposure (AUC) when compared to administration after a meal.
After a 800mg dose of radio-labelled etraverine, 93.7% was found to undergo fecal elimination, with 81.2% - 86.4% eliminated unchanged. 1.2% of the dose was renally eliminated, changed. Etravirine is dialyzable (hemodialysis).
Distribution of etravirine into compartments other than plasma has not been evaluated in humans.
Renal clearance of etravirine is negligible (<1.2%), thus no dose adjustments are required in patients with renal impairment. Clearance is shown to be reduced in patients with Hepatitis B and/or co-infection, however, the safety profile of etravirine does not call for dosage adjustments.

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Metabolism / Metabolites
Metabolized (in vitro) by the liver CYP450 enzymes: CYP3A4, CYP2C9, CYP2C19. The major metabolites formed by a methyl hydroxylation of the dimethylbenzonitrile moiety retained less than 90% of etravirine's activity.

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Biological Half-Life
Half life of 9.05-41 hours.

Hepatotoxicity
Serum aminotransferase elevations occur in a high proportion of patients on etravirine therapy, but increases above 5 times the upper limit of normal occur in only 2% to 3% of patients; this rate may be higher in patients who have hepatitis C coinfection. In most studies, the rate of liver enzyme elevations was no different in etravirine treated than among in comparator arms. In large clinical trials as well as open access studies, there were no reported instances of clinically apparent liver injury attributed to etravirine.
Skin rashes occur in 10% to 20% of patients on etravirine usually during the first 2 to 6 weeks of therapy, and this rate is higher than with other antiretroviral regimens or comparator arms and is the major reason for discontinuation of etravirine because of adverse events. The skin rash during etravirine therapy can be accompanied by other signs of hypersensitivity including Stevens Johnson Syndrome and immunoallergic hepatitis. Clinically apparent hepatotoxicity is rare, but cases of hepatitis accompanying rash and signs of hypersensitivity have been reported to the sponsor, some of which have resulted in fatalities. The clinical features of these cases have not been described in detail. Most cases of hypersensitivity hepatitis due to nonnucleoside reverse transcriptase inhibitors arise during the first 6 weeks of therapy and are accompanied by immunoallergic manifestations such as rash, fever, lymphadenopathy and eosinophilia. Recovery is usually prompt after discontinuation, but progressive fatal instances of liver injury can occur.
Likelihood score: D (possible cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Etravirine is excreted in breastmilk in concentrations exceeding the maternal plasma and appears to increase in concentration over time. Until more information becomes available, an alternate agent may be preferred. Achieving and maintaining viral suppression with antiretroviral therapy decreases breastfeeding transmission risk to less than 1%, but not zero. Individuals with HIV who are on antiretroviral therapy with a sustained undetectable viral load and who choose to breastfeed should be supported in this decision. If a viral load is not suppressed, banked pasteurized donor milk or formula is recommended.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Plasma protein binding is about 99.9% in vitro. In vitro, 99.6% is bound to albumin, and 97.66% - 99.02% is bound to 1-alpha glycoprotein.

[1]. TMC125, a novel next-generation nonnucleoside reverse transcriptase inhibitor active against nonnucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus type 1. Antimicrob Agents Chemother, 2004. 48(12): p. 468.

[2]. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-2: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet, 2007. 370(9581): p. 39-48.

Pharmacodynamics
Clinical trials have shown no prolongation of QT intervals on electrocardiograms after 8 days of dosing.

C20H15BRN6O

435.28

434.049

269055-15-4

Etravirine-d4;1142095-93-9;Etravirine-d8;1142096-06-7

193962

White to off-white solid powder

1.6±0.1 g/cm3

637.4±65.0 °C at 760 mmHg

265ºC (dec.)

339.3±34.3 °C

0.0±1.9 mmHg at 25°C

1.703

4.19

120.64

2

7

4

28

609

0

PYGWGZALEOIKDF-UHFFFAOYSA-N

InChI=1S/C20H15BrN6O/c1-11-7-14(10-23)8-12(2)17(11)28-19-16(21)18(24)26-20(27-19)25-15-5-3-13(9-22)4-6-15/h3-8H,1-2H3,(H3,24,25,26,27)

4-(6-Amino-5-bromo-2-(4-cyanoanilino)pyrimidin-4-yloxy)-3,5-dimethylbenzonitrile

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)

配方 1 中的溶解度: ≥ 2.5 mg/mL (5.74 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (5.74 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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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。