HSV-1(EC50=0.5 μg/mL);HSV-2(EC50=0.8 μg/mL)

Penciclovir (BRL-39123) 抑制单纯疱疹病毒 1 型 (HSV-1) 和 2 型 (HSV-2)、水痘带状疱疹病毒 (VZV)、EB 病毒 (EBV)、人巨细胞病毒 (HCMV)，IC50 为分别为0.04-1.8μg/mL、0.06-4.4μg/mL、1.6-8μg/mL、1.5-3.1μg/mL、51μg/mL。喷昔洛韦 (PCV) 是一种无环鸟嘌呤衍生物（不作为口服药物市售），具有与阿昔洛韦 (ACV) 相似的活性谱和作用机制[1]。

喷昔洛韦（100 mg/kg；皮下注射；每天一次，持续 5 天）可预防小鼠死亡[2]。

人乳腺癌细胞系 MCF-7 和 MDA-MB-435、胶质母细胞瘤 U87MG 和胚胎肾细胞 293T 在 37°C、含 5% CO2 的潮湿气氛中在 Iscove 改良的 Dulbecco 培养基或 Leibovitz's L 培养基和 5% 培养基中培养胎牛血清（FBS）。进行的测定略有修改。简而言之，将细胞接种到 24 孔板（5×104 个细胞/孔）中，48 小时后用每个细胞 103 个未修饰病毒 (Adtk)、聚乙二醇化病毒 (PEG-Adtk) 或 RGD-PEG 修饰病毒颗粒进行感染病毒 (RGD-PEG-Adtk) 在含有 2% FBS 的培养基中一式三份，并在 37°C 下孵育 4 小时。然后用正常培养基替换孵育培养基并将细胞进一步孵育48小时。收获细胞并用 500 μL TK 裂解缓冲液裂解，其中含有 0.5% Nonidet P-40 (NP-40)、20 mM N-(2-羟乙基)哌嗪-N'-(2-乙磺酸) (HEPES) ( pH 7.6)、2 mM Mg(OAc)2、1 mM 二硫苏糖醇和 50 μM 胸苷。离心后收集上清液。样品在使用前保存在-80°C。通过 Micro BCA 测定法测定修饰和未修饰的腺病毒蛋白浓度。将一微克细胞提取物与 HSV1-tk 底物 8-3H-喷昔洛韦 (8-3 H-PCV) 一起孵育。使用 DE-81 过滤器将磷酸化示踪剂与未磷酸化 8-3 H-PCV 分离。 TK 活性表示为每分钟每微克蛋白质底物转化的百分比[2]。

Animal Model: Three-week-old female Balb/c mice[2]
Dosage: 100 mg/kg
Administration: S.c.; daily for 5 days
Result: decreased viral titres in the respiratory systems of mice infected with PR3 and W/t.

Absorption, Distribution and Excretion
Measurable penciclovir concentrations were not detected in plasma or urine of healthy male volunteers (n= 12) following single or repeat application of the 1% cream at a dose of 180 mg penciclovir daily.
Measurable penciclovir concentrations were not detected in plasma or urine of healthy male volunteers (n=12) following single or repeat application of the 1% cream at a dose of 180 mg penciclovir daily (approximately 67 times the estimated usual clinical dose).
There is no information on whether penciclovir is excreted in human milk after topical administration. However, following oral administration of famciclovir (the oral prodrug of penciclovir) to lactating rats, penciclovir was excreted in breast milk at concentrations higher than those seen in the plasma.
The ... pharmacokinetics of intravenously administered penciclovir (BRL 39,123A), a novel anti-herpes agent, were investigated in 15 healthy male subjects. The volunteers were divided into three groups, receiving either 10, 15 or 20 mg/kg penciclovir by a 60 min constant-rate infusion. Blood samples were taken sequentially up to 48 hr after the start of the infusion and urine collections made at appropriate intervals up to 72 hr. After a simple solid phase extraction, concentrations of penciclovir in plasma and urine were determined using HPLC with U.V. detection. Mean values of Cmax, corresponding usually with the end of infusion, and of AUC appeared to increase proportionately with dose. Furthermore, there was no evidence that dose significantly affected any individual pharmacokinetic parameter. Penciclovir was distributed into tissues with an overall mean volume of distribution of approximately 1.5 L.kg-1, i.e. approximately double that of body water. It was rapidly eliminated, with a mean total plasma clearance of 39.3 L.hr-1, and a mean terminal-phase half-life of 2.0 hr. The majority of the dose, approximately 70%, was excreted unchanged in the urine. Mean renal clearance of BRL 39,123 was 28.1 L.hr-1, which exceeds normal glomerular filtration rate and approaches renal plasma flow.
Following the oral administration of a single 500 mg dose of radiolabeled famciclovir to three healthy male volunteers, 73% and 27% of administered radioactivity were recovered in urine and feces over 72 hours, respectively. Penciclovir accounted for 82% and 6-deoxy penciclovir accounted for 7% of the radioactivity excreted in the urine. Approximately 60% of the administered radiolabeled dose was collected in urine in the first 6 hours.
For more Absorption, Distribution and Excretion (Complete) data for Penciclovir (15 total), please visit the HSDB record page.

---

Metabolism / Metabolites
Hepatic
Following oral administration, famciclovir is deacetylated and oxidized to form penciclovir. Metabolites that are inactive include 6-deoxy penciclovir, monoacetylated penciclovir, and 6-deoxy monoacetylated penciclovir (5%, <0.5% and <0.5% of the dose in the urine, respectively). Little or no famciclovir is detected in plasma or urine. An in vitro study using human liver microsomes demonstrated that cytochrome P450 does not play an important role in famciclovir metabolism. The conversion of 6-deoxy penciclovir to penciclovir is catalyzed by aldehyde oxidase.
Famciclovir is deacetylated and oxidized to penciclovir. Penciclovir is phosphorylated to penciclovir triphosphate (the active metabolite) in cells infected with HSV-1, HSV-2, or VZV. The inactive metabolite 6-deoxy penciclovir is converted to penciclovir by aldehyde oxidase. Famciclovir not metabolized by CYP enzymes.

---

Biological Half-Life
2 hours
Elimination half-life of penciclovir after oral administration of famciclovir 1.6-3 hours. Intracellular half-life of penciclovir triphosphate in cells infected with herpes simplex virus (HSV)-1 or HSV-2 is 10 and 20 hours, respectively; intracellular half-life in varicella zoster virus (VZV)-infected cells is 7-14 hours.
The ... pharmacokinetics of intravenously administered penciclovir (BRL 39,123A), a novel anti-herpes agent, were investigated in 15 healthy male subjects. A mean terminal-phase half-life of 2.0 hr /was reported/.
The plasma elimination half-life of penciclovir was 2.0 + or - 0.3 hours after intravenous administration of penciclovir to 48 healthy male volunteers and 2.3 + or - 0.4 hours after oral administration of 500 mg famciclovir to 124 healthy male volunteers. The half-life in 17 patients with herpes zoster was 2.8 + or - 1.0 hours and 2.7 + or - 1.0 hours after single and repeated doses, respectively.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Although there is no published experience with penciclovir during breastfeeding, infant side effects are unlikely with maternal topical application to small areas of the mother's body away from the breast. Only water-miscible cream or gel products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking.[1]
◉ 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.

---

Protein Binding
Less than 20%.

[1]. Penciclovir: a review of its spectrum of activity, selectivity, and cross-resistance pattern. Antiviral Chemistry and Chemotherapy, 1993, (1): 3-11.

[2]. The acyclic nucleoside analogue penciclovir is a potent inhibitor of equine herpesvirus type 1 (EHV-1) in tissue culture and in a murine model. Antiviral Res. 1992 May;18(1):77-89.

Therapeutic Uses
Antiviral Agents; Reverse Transcriptase Inhibitors
Denavir (penciclovir cream) is indicated for the treatment of recurrent herpes labialis (cold sores) in adults and children 12 years of age and older. /Included in US product label/

---

Drug Warnings
Denavir should only be used on herpes labialis on the lips and face. Because no data are available, application to human mucous membranes is not recommended. Particular care should be taken to avoid application in or near the eyes since it may cause irritation. Lesions that do not improve or that worsen on therapy should be evaluated for secondary bacterial infection. The effect of Denavir has not been established in immunocompromised patients.
FDA Pregnancy Risk Category: B /NO EVIDENCE OF RISK IN HUMANS. Adequate, well controlled studies in pregnant women have not shown increased risk of fetal abnormalities despite adverse findings in animals, or, in the absence of adequate human studies, animal studies show no fetal risk. The chance of fetal harm is remote but remains a possibility./
There is no information on whether penciclovir is excreted in human milk after topical administration. However, following oral administration of famciclovir (the oral prodrug of penciclovir) to lactating rats, penciclovir was excreted in breast milk at concentrations higher than those seen in the plasma. Therefore, a decision should be made whether to discontinue the drug, taking into account the importance of the drug to the mother.
In 74 patients >/=65 years of age, the adverse events profile was comparable to that observed in younger patients.
For more Drug Warnings (Complete) data for Penciclovir (9 total), please visit the HSDB record page.

---

Pharmacodynamics
Penciclovir is the active metabolite of the oral product famciclovir. The more favorable results observed with topical penciclovir versus topical acyclovir for the treatment of herpes labialis may be due to the longer intracellular half-life of penciclovir in HSV-infected cells. The activated drug inhibits the viral DNA polymerase. This impairs the ability of the virus to replicate within the cell.

C10H15N5O3

253.26

253.117

C, 47.42; H, 5.97; N, 27.65; O, 18.95

39809-25-1

Penciclovir-d4;1020719-72-5;Penciclovir sodium;97845-62-0

135398748

White crystalline solid from water (monohydrate) ... also reported as colorless matted needles

1.7±0.1 g/cm3

636.7±65.0 °C at 760 mmHg

275-277°C

338.9±34.3 °C

0.0±2.0 mmHg at 25°C

1.749

-3.58

130.05

4

5

5

18

344

0

O([H])C([H])([H])C([H])(C([H])([H])O[H])C([H])([H])C([H])([H])N1C([H])=NC2C(N([H])C(N([H])[H])=NC1=2)=O

JNTOCHDNEULJHD-UHFFFAOYSA-N

InChI=1S/C10H15N5O3/c11-10-13-8-7(9(18)14-10)12-5-15(8)2-1-6(3-16)4-17/h5-6,16-17H,1-4H2,(H3,11,13,14,18)

2-amino-9-[4-hydroxy-3-(hydroxymethyl)butyl]-3H-purin-6-one

BRL-39123; BRL 39123; BRL39123; VSA 671; VSA671; VSA-671; Penciclovir; Denavir, Vectavir and Fenivir.

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 : 25~34 mg/mL (98.71~134.24 mM)
H2O : ~2 mg/mL (~7.90 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (9.87 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。

---

配方 2 中的溶解度: ≥ 2.5 mg/mL (9.87 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in 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900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

---

View More

配方 3 中的溶解度: ≥ 2.5 mg/mL (9.87 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。

---

配方 4 中的溶解度: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (9.87 mM)

---

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。