HSV-1 (IC50 = 2.9 μg/mL)

根据 Michaelis-Menten 常数，Valaciclovir (VACV) 的最大速率分别为 23.34 nmol/mg 蛋白质/5 分钟和 1.64 mM，具有浓度依赖性和饱和吸收。大鼠、兔和 Caco-2 细胞以及 hPEPT1/CHO 细胞中的 Km 值非常相似，表明 hPEPT1 控制 VACV 的体外肠道转运特性 [5]。

一项重要的比较试验发现，对于治疗首次发作的生殖器疱疹，伐昔洛韦（1 g，每天两次）持续 10 天与阿昔洛韦（200 mg，每天 5 次）一样有效。两项试验发现，在为期五天的治疗周期中，伐昔洛韦（200 毫克，每日五次）与阿昔洛韦（200 毫克，每日五次）对于控制复发同样有效。伐昔洛韦每天 1 克的剂量与每天 2 克的效果相同。每天可以给予一剂伐昔洛韦[1]。口服伐昔洛韦 1,000 mg，每天 3 次，六天后，在稳态下评估血清和脑脊液阿昔洛韦浓度 [2]。 PE 和 AC 在 3T3 细胞中的 EC50 值分别为 0.02 和 0.01 ug/ml，但在 BHK 细胞中分别为 0.2 和 0.03 ug/ml。用FA和VA治疗感染的免疫抑制小鼠（每天两次，5.5天）以消除耳轻瘫、耳部病变（水泡等）和死亡。红斑比例也从 100% 降低至 24% 和 38%。到第六天，病毒已经从耳朵和脑干消失，但在接受 VA 治疗的小鼠中，当药物停止时，病毒又回来了 [3]。

通过使用斑块减少测定法测定HSV-1W菌株的体外50%抑制浓度（IC50），以验证其对阿昔洛韦的敏感性。HSV-1 W的IC50测定为2.9µg/ml[4]。

我们实验室先前使用原位灌注技术在大鼠和兔顶端刷状边界膜囊泡中进行的研究结果表明，缬环鸟苷（VACV）的肠道摄取似乎是由多种膜转运蛋白介导的。使用这些技术，在存在多种已知或未知转运蛋白的情况下，很难表征VACV与每个单独转运蛋白的转运动力学。本研究的目的是使用过表达人肠肽转运蛋白（hPEPT1）基因的中国仓鼠卵巢（CHO）细胞来表征VACV与人肠肽转运体的相互作用。用hPEPT1转染的CHO细胞中的VACV摄取显著高于仅用载体pcDNA3转染的细胞。VACV吸收的最佳pH确定为在pH 7.5时发生。在hPEPT1/CHO细胞中未观察到质子共转运，这与先前在组织和Caco-2细胞中观察到的结果一致。VACV摄取是浓度依赖性的，并且可饱和，米氏常数和最大速度分别为1.64+/-0.06mM和23.34+/-0.36nmol/mg蛋白质/5min。在hPEPT1/CHO细胞、大鼠和兔组织以及Caco-2细胞中获得了非常相似的Km值，表明hPEPT1在体外主导VACV的肠道运输特性。VACV的摄取被各种二肽和β-内酰胺类抗生素显著抑制，在pH 7.5时，Gly-Sar和头孢羟氨苄的Ki值分别为12.8+/-2.7和9.1+/-1.2mM。目前的结果表明，VACV是hPEPT1/CHO细胞中人类肠肽转运蛋白的底物，并且尽管转运是pH依赖性的，但质子协同转运并不明显。此外，结果表明hPEPT1/CHO细胞系统可用于研究药物与人肠肽转运蛋白hPEPT1的转运动力学；然而，将这些转运特性外推到体内情况需要进一步研究[5]。

Acyclovir has been a frequently used antiviral agent in the clinical treatment of leukemia, acute encephalitis, malignant tumor and herpes simplex. The adverse effects of this drug have been widely described in clinical practice. In the present study, a case of a 35-year-old female patient diagnosed with herpes simplex, who developed acute renal injury following treatment with valacyclovir hydrochloride, is described. Kidney biopsy, light microscopy and laboratory examination were performed, and all findings revealed the signs of evident vacuolar degeneration of capillary endothelial and renal tubular epithelial cells, erythrocyte aggregation in partial renal tubule and microvilli exfoliation from epithelial cells. Renal interstitial edema was clearly identified. The clinical evidence observed from this female patient indicated that renal functions should be closely monitored during valacyclovir hydrochloride administration. A variety of effective measures, such as hydration, alkalizing urine, promoting the discharge of medication and the use of antagonists are recommended following the administration of antiviral agents[1].

Absorption, Distribution and Excretion
Following oral administration, valacyclovir hydrochloride is rapidly absorbed from the gastrointestinal tract and converted to acyclovir and L-valine. In 12 healthy subjects, after oral administration of 1 gram of valacyclovir and intravenous injection of 350 mg of acyclovir, the absolute bioavailability of acyclovir was measured to be 54.5% ± 9.1%. The bioavailability of acyclovir (a metabolite of valacyclovir) was not affected by food. In 4 healthy subjects, following a single oral administration of 1 gram of radiolabeled valacyclovir, 46% and 47% of the administered radioactivity were detected in urine and feces, respectively, within 96 hours. Acyclovir accounted for 89% of the radioactive material excreted in urine.
The cerebrospinal fluid (CSF) permeability (determined by the CSF/plasma AUC ratio) is approximately 25% for acyclovir and its metabolite 8-hydroxyacyclovir (8-OH-ACV), and approximately 2.5% for its metabolite 9-(carboxymethoxy)methylguanine. In a study of immunocompromised pediatric patients, the volume of distribution of valacyclovir at a dose of 15 ml/kg was 1.34 ± 0.65 L/kg.
Following a single 1-g valacyclovir dose in 12 healthy volunteers, the renal clearance of acyclovir was approximately 255 ± 86 mL/min, representing 42% of the total apparent plasma clearance of acyclovir.
After oral administration, valacyclovir hydrochloride is rapidly absorbed from the gastrointestinal tract and almost completely converted to acyclovir and L-valine via first-pass metabolism in the intestine and/or liver. In 12 healthy volunteers, the absolute bioavailability of acyclovir was 54.5% ± 9.1% after oral administration of 1 g valacyclovir and intravenous administration of 350 mg acyclovir. The bioavailability of acyclovir via valacyclovir (Valtrex) was not affected by food (873 kcal breakfast containing 51 g fat, taken 30 minutes later). The binding rate of valacyclovir to human plasma proteins ranged from 13.5% to 17.9%. The binding rate of acyclovir to human plasma proteins ranged from 9% to 33%. The pharmacokinetic distribution of acyclovir administered with valacyclovir was consistent with previous experience with intravenous and oral acyclovir. In 4 healthy subjects, following a single oral dose of 1 g of radiolabeled valacyclovir, 46% and 47% of the radioactive material were excreted in urine and feces, respectively, within 96 hours. Of the radioactive material excreted in urine, 89% was acyclovir. Following a single administration of 1 gvalacyclovir to 12 healthy volunteers, the renal clearance of acyclovir was approximately 255 ± 86 mL/min, representing 42% of the total apparent plasma clearance of acyclovir. The intestinal transport mechanism of valacyclovir, an L-valine ester prodrug of acyclovir, was investigated in rats using in situ intestinal perfusion. Results indicated that the oral bioavailability of valacyclovir appeared to be significantly affected by factors such as the conversion of valacyclovir to malabsorbable acyclovir before absorption; the involvement of multiple transport proteins in the absorption of valacyclovir in the small intestine; and the low permeability of valacyclovir in the colon. In 5 lactating women, after oral administration of 500 mg valacyclovir, the peak concentration (Cmax) of acyclovir in breast milk was 0.5 to 2.3 times the corresponding maternal serum acyclovir concentration (median 1.4 times). The AUC of acyclovir in breast milk is 1.4 to 2.6 times that in maternal serum (median 2.2 times). A maternal dose of 500 mg valacyclovir twice daily provides a nursing infant with approximately 0.6 mg/kg/day of oral acyclovir. This results in a nursing infant exposure that is less than 2% of the standard intravenous dose of acyclovir (30 mg/kg/day) given to newborns. Unmetabolized valacyclovir was not detected in maternal serum, breast milk, or infant urine.

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Metabolism/Metabolites
Valacyclovir is first-pass metabolized in the intestine and/or liver to acyclovir and L-valine. Acyclovir is metabolized by alcohol dehydrogenases and aldehyde dehydrogenases, and a small amount is converted to an inactive metabolite by aldehyde oxidase. Neither valacyclovir nor acyclovir is metabolized by cytochrome P450 enzymes.
…The major metabolite of acyclovir is 9-carboxymethoxymethylguanine. Valacyclovir undergoes first-pass metabolism in the intestine and/or liver to acyclovir and L-valine. A small amount of acyclovir is converted to inactive metabolites by aldehyde oxidase and alcohol-aldehyde dehydrogenase. Neither valacyclovir nor acyclovir is metabolized by cytochrome P450 enzymes. Unconverted valacyclovir plasma concentrations are low and transient, usually unquantifiable within 3 hours after administration. Peak plasma concentrations of valacyclovir are typically below 0.5 μg/mL at all doses. After a single dose of 1 g valacyclovir, the mean plasma valacyclovir concentrations in patients with hepatic impairment, renal insufficiency, and healthy volunteers concurrently taking cimetidine and probenecid were 0.5, 0.4, and 0.8 μg/mL, respectively.

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Biological Half-Life
In multiple valacyclovir studies in volunteers with normal renal function, the plasma elimination half-life of acyclovir typically ranged from 2.5 to 3.3 hours.
In all valacyclovir studies in volunteers with normal renal function, the plasma elimination half-life of acyclovir typically ranged from 2.5 to 3.3 hours.

Hepatotoxicity
Oral valacyclovir treatment is associated with a low incidence of mild to moderate elevations in serum transaminases, but these abnormalities are usually asymptomatic and resolve spontaneously even with continued treatment. However, because enzyme elevations are not uncommon during varicella-zoster virus infection (including chickenpox and shingles) and can progress to clinically manifested hepatitis or even acute liver failure, it is difficult to attribute liver dysfunction to valacyclovir treatment. Clinically manifested liver disease caused by valacyclovir itself is rare, but case reports exist. Case 1 had a short onset time (1 to 2 weeks), a mild course, few symptoms, and rapid resolution. The described liver injury pattern was mixed hepatocellular-cholestatic. No immune hypersensitivity features or autoantibodies were found. Probability score: D (likely a rare cause of clinically manifested liver injury).

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Effects during pregnancy and lactation
◉ Overview of use during lactation
After valacyclovir administration, the dose of acyclovir in breast milk is less than 1% of the typical infant dose, and no adverse effects are expected on breastfed infants. No special precautions are required for the use of valacyclovir during lactation. One study showed that valacyclovir administration to mothers co-infected with herpes simplex virus type 2 and HIV reduced HIV shedding in breast milk at 6 and 14 weeks postpartum, but this effect was not observed thereafter. [1] In another study of HIV-positive mothers, valacyclovir did not reduce cytomegalovirus (CMV) shedding in breast milk or the risk of CMV infection in infants. [2]
◉ Effects on breastfed infants
In a study of pregnant women co-infected with HIV and herpes simplex virus, the mothers received 300 mg of zidovudine daily from week 34 of pregnancy to 12 months postpartum and nevirapine at delivery. Half of the women (n = 74) received 500 mg valacyclovir orally twice daily from 34 weeks of gestation to 12 months postpartum. At 6 weeks postpartum, all infants who received acyclovir via breast milk had normal serum creatinine levels (<0.83 mg/dL). Except for one infant with an ALT level of 70.1 units/L, the median serum creatinine and alanine aminotransferase (ALT) levels, as well as growth and development, were not different from those of infants who had not been exposed to valacyclovir. Infants whose mothers received valacyclovir generally experienced similar adverse reactions to those in the placebo group, but the treated infants had a lower risk of eczema and thrush than the placebo group. [1][4]
◉ Effects on lactation and breast milk
No relevant published information was found as of the revision date.

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Protein binding
Valacyclovir had low binding rates to human plasma proteins, ranging from 13.5% to 17.9%.

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Interactions
Valacyclovir co-administration with probenecid may increase the peak plasma concentration and AUC of acyclovir. This pharmacokinetic interaction is not clinically significant in patients with normal renal function, therefore no dose adjustment is required.
Valacyclovir co-administration with cimetidine may increase the peak plasma concentration and AUC of acyclovir. This pharmacokinetic interaction is not clinically significant in patients with normal renal function, therefore no dose adjustment is required.
Mycophenolate mofetil (MMF) is a drug that can reduce the incidence of kidney transplant rejection. However, cytomegalovirus infection is a common complication of this treatment, so doctors often prescribe antiviral prophylaxis drugs such as valacyclovir. Neutropenia may occur during this combination therapy, but the cause of this adverse reaction is difficult to determine. This report presents a case of neutropenia in a woman receiving MMF and valacyclovir treatment. Because the duration of valacyclovir treatment perfectly coincided with the duration of neutropenia, and the mycophenolate mofetil trough concentration increased with rising neutrophil counts, neutropenia was initially thought to be caused by valacyclovir. However, after reviewing case reports of neutropenia in the literature, an interaction between mycophenolate mofetil and valacyclovir is suspected. Mycophenolate mofetil may increase intracellular valacyclovir concentrations to hematologic toxic levels. This mechanism may explain the interaction between the two, but further research is needed to confirm it.

[1]. Valacyclovir. New indication: for genital herpes, simpler administration. Can Fam Physician. 1999 Jul;45:1698-700, 1703-5.

[2]. Acyclovir levels in serum and cerebrospinal fluid after oral administration of valacyclovir. Antimicrob Agents Chemother. 2003 Aug;47(8):2438-41.

[3]. Comparison of efficacies of famciclovir and valaciclovir against herpes simplex virus type 1 in a murineimmunosuppression model. Antimicrob Agents Chemother. 1995 May;39(5):1114-9.

[4]. Dhaliwal DK, Romanowski EG, Yates KA, Valacyclovir inhibits recovery of ocular HSV-1 after experimental reactivation by excimer laser keratectomy. Cornea. 1999 Nov;18(6):693-9.

[5]. Guo A, Hu P, Balimane PV, Interactions of a nonpeptidic drug, valacyclovir, with the human intestinal peptide transporter (hPEPT1) expressed in a mammalian cell line.J Pharmacol Exp Ther. 1999 Apr;289(1):448-54.

Therapeutic Uses
Antiviral Drugs
Oral valacyclovir is used to treat cases of initial infection with genital herpes simplex virus (HSV-2) in immunocompetent adults and adolescents. Because many patients with initial genital herpes infection experience mild clinical symptoms that later develop into severe or prolonged symptoms, the Centers for Disease Control and Prevention (CDC) states that most patients with initial genital herpes infection should receive antiviral treatment. /US Product Label Includes/
Oral valacyclovir is used to treat cases of recurrent genital herpes in immunocompetent adults and adolescents. Antiviral treatment for recurrent genital herpes can be administered intermittently to reduce or shorten the course of the disease, or continuously as a suppressive therapy to reduce the frequency of recurrences. /US Product Label Includes/
Valacyclovir is used to treat intermittent outbreaks of cold sores (perioral herpes, labial herpes, vesicular herpes) in adults and adolescents. /US Product Label Includes/
For more complete data on the therapeutic uses of valacyclovir (out of 9), please visit the HSDB record page.

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Drug Warning
Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) has occurred in patients with advanced HIV-1 infection and allogeneic bone marrow and kidney transplant recipients in clinical trials of valacyclovir (8 g daily), with some cases even resulting in death. If clinical signs, symptoms, and laboratory abnormalities consistent with TTP/HUS occur, valacyclovir should be discontinued immediately.

There are currently no adequate and well-controlled studies on the use of valacyclovir or acyclovir in pregnant women. Based on prospective pregnancy registry data from 749 pregnancies, the overall incidence of birth defects in infants exposed to acyclovir in utero appears to be similar to that in the general population. Valacyclovir should only be used during pregnancy if the potential benefit outweighs the potential risk to the fetus.

Acute renal failure has been reported in the following situations: 1. Elderly patients, regardless of renal impairment. Caution should be exercised when using valacyclovir in elderly patients, and dose reduction is recommended for patients with impaired renal function.
2. Patients with underlying kidney disease who are receiving a dose of valacyclovir higher than the recommended dose for their renal function level. A dose reduction of valacyclovir is recommended for patients with impaired renal function. 3. Patients taking other nephrotoxic medications. Caution should be exercised when using valacyclovir in patients taking potentially nephrotoxic medications. 4. Patients who are not adequately hydrated. Acyclovir may precipitate in the renal tubules when the solubility of acyclovir in the tubular fluid (2.5 mg/mL) exceeds its solubility. All patients should maintain adequate hydration.
The most common adverse reactions occurring in more than 10% of adult patients treated with valacyclovir for at least one indication and more common than placebo are headache, nausea, and abdominal pain. The only reported adverse reaction occurring in more than 10% of pediatric patients under 18 years of age is headache.
For more complete data on drug warnings for valacyclovir (8 of 8), please visit the HSDB record page. Pharmacodynamics Antibacterial Effects Valacyclovir exhibits varying degrees of inhibition against herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). The quantitative relationship between the sensitivity of herpesviruses to antiviral drugs in cell culture and clinical response to the same antiviral therapy in humans has not been elucidated. Sensitivity test results, described as the drug concentration required to inhibit viral growth by 50% in cell culture (EC50), can vary considerably due to various factors. Clinical Study Results The following is a summary of clinical study results for various diseases: _Herpes labialis_ Immunocompromised patients with herpes labialis were observed using either a 1-day course (2 g valacyclovir twice daily for 1 day, followed by a placebo for 1 day) or a 2-day course (2 g valacyclovir twice daily for 2 consecutive days). Compared to the placebo group, the treatment group had a shortened mean duration of cold sore throat flare-ups by approximately one day. A two-day course of valacyclovir did not show superior efficacy compared to a one-day course. No clinically significant difference was observed between the valacyclovir and placebo groups in preventing post-papular progression of cold sore throat lesions, suggesting that the timing of valacyclovir administration is an important consideration. First Genital Herpes Outbreak: A double-blind trial randomized 643 immunocompetent adult patients who presented with their first genital herpes symptoms within 72 hours of symptom onset. Patients were randomly assigned to receive either 10 days of valacyclovir treatment (1 g twice daily, n=323) or oral acyclovir (200 mg five times daily, n=320). The median time to healing of herpes lesions was 9 days in both groups, the median time to pain relief was 5 days, and the median time to viral shedding was approximately 3 days. _Recurrent Genital Herpes_ Results from three independent studies showed that patients receiving a 3- to 5-day course of valacyclovir recovered on average in 4 days, experienced relief of lesion-related pain in 2 to 3 days, and stopped viral shedding on average in 2 days. These results indicate that valacyclovir treatment is significantly more effective than placebo. Regarding Drug Resistance Resistance to acyclovir in herpes simplex virus and varicella-zoster virus may stem from qualitative and quantitative changes in viral thymidine kinase (TK) and/or DNA polymerase. Clinical isolates of varicella-zoster virus (VZV) with reduced susceptibility to acyclovir have been isolated from HIV patients. A total of 522 TK-deficient VZV mutant strains were identified in these cases.

C13H20N6O4

324.341

324.154

C, 48.14; H, 6.22; N, 25.91; O, 19.73

124832-26-4

Valacyclovir hydrochloride;124832-27-5;Valacyclovir hydrochloride hydrate;1218948-84-5

135398742

Typically exists as solid at room temperature

1.5±0.1 g/cm3

170-172

309.7ºC

1.673

-0.88

151.14

3

7

8

23

483

1

N[C@@H](C(C)C)C(OCCOCN1C=NC2=C1N=C(N)NC2=O)=O

HDOVUKNUBWVHOX-QMMMGPOBSA-N

InChI=1S/C13H20N6O4/c1-7(2)8(14)12(21)23-4-3-22-6-19-5-16-9-10(19)17-13(15)18-11(9)20/h5,7-8H,3-4,6,14H2,1-2H3,(H3,15,17,18,20)/t8-/m0/s1

2-((2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy)ethyl L-valinate

BW-256U87; BW-256; BW256256U87 hydrochloride; BW 256 Val-ACV; Valtrex; Zelitrex; Valacyclovir HCl; Valacyclovir hydrochloride; ValACV; Zelitrex; Valcivir; Valcyclovir; Val-ACV;

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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;
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