HSV-1 (IC50 = 2.9 μg/mL)
Herpes simplex virus (HSV). Valacyclovir is the metabolic precursor (prodrug) of acyclovir, which is an antiviral drug active against herpes simplex viruses. [1]

At concentrations of 1.64 mM and 23.34 nmol/mg protein/5 min, respectively, the maximal rates of valacyclovir hydrochloride (valaciclovir hydrochloride, VACV) uptake are concentration-dependent and saturable. The in vitro intestinal transport properties of VACV are dominated by hPEPT1, as demonstrated by the very identical Km values observed in hPEPT1/CHO cells, rat and rabbit tissues, and Caco-2 cells [5].

---

A major comparative trial found that valacyclovir hydrochloride (1 g twice daily) for 10 days was just as effective as acyclovir (200 mg 5 times daily) for treating a first bout of genital herpes. Two trials found that valacyclovir (200 mg five times daily) was equally efficacious as acyclovir (200 mg five times daily) in a five-day treatment cycle for managing relapses. Valacyclovir at a dose of 1 g per day works just as well as 2 g per day. One dose of valacyclovir can be given every day [1]. Serum and cerebrospinal fluid acyclovir concentrations were assessed at steady state following six days of oral valacyclovir 1,000 mg three times a day [2]. PE and AC have EC50 values in 3T3 cells of 0.02 and 0.01 ug/ml, however in BHK cells they are 0.2 and 0.03 ug/ml. Immunosuppressed mice that were infected were treated with FA and VA (bid, 5.5 days) to eradicate otoparesis, ear lesions (vesicles, etc.), and death. The percentage of erythema was also reduced from 100% to 24% and 38%. By day six, the virus had vanished from the ears and brainstem, but in mice receiving VA treatment, it returned when the medication was stopped [3].

---

For the treatment of a first episode of genital herpes, a large comparative trial involving 643 patients showed that valacyclovir (1 g twice a day for 10 days) is as effective as acyclovir (200 mg five times a day for 10 days). The median time for lesions to heal was 9 days for both drugs, the median duration of pain was 5 days, and the median duration of viral shedding was 3 days. [1]
For the treatment of recurrent genital herpes, multiple trials have demonstrated the efficacy of valacyclovir.
One trial with 1200 patients compared valacyclovir (1 g twice a day), acyclovir (200 mg five times a day), and placebo. Both antiviral drugs were equally effective in reducing the time required for lesions to heal and were more effective than placebo. [1]
Another trial with 739 patients compared valacyclovir (500 mg twice a day for 5 days) and acyclovir (200 mg five times a day for 5 days). The time required for lesions to heal and for pain to disappear was equivalent for both treatments. [1]
A dose-ranging trial with 987 patients showed that 500 mg twice a day and 1000 mg twice a day of valacyclovir for 5 days were equally effective, with a median episode duration of 4 days for both doses, compared to 6 days for placebo. Valacyclovir was also more effective than placebo in reducing the frequency of aborted episodes and the duration of pain. [1]
A trial with 922 patients demonstrated that a daily dose of 1 g of valacyclovir given in either one or two doses had equivalent efficacy. [1]
For the prevention (suppression) of recurrent genital herpes, a double-blind, placebo-controlled trial involving 382 patients with at least eight yearly episodes showed that valacyclovir (500 mg once daily) was significantly more effective than placebo. After 16 weeks of treatment, 69% of patients in the valacyclovir group had no new acute episodes, compared to 9.5% in the placebo group (P < .0001). [1]

The in vitro 50% inhibitory concentration (IC50) of HSV-1 W strain was determined by using a plaque-reduction assay to verify its sensitivity to acyclovir. The IC50 for HSV-1 W was determined to be 2.9 µg/ml. [4].

---

Forty-seven NZW rabbits latently infected with HSV-1 W strain were divided into four groups: I, 50 mg/kg/day valacyclovir; II, 100 mg/kg/day valacyclovir; III, 150 mg/kg/day valacyclovir; and IV, saline control. One half of the total dose of valacyclovir was delivered via intraperitoneal injections twice daily for 7 days beginning with one dose before excimer laser keratectomy. HSV-1 ocular shedding was determined from eye cultures for 7 days after treatment.The administration of both 100 mg/kg/day (group II) and 150 mg/kg/day (group III) of valacyclovir significantly reduced the number of eyes from which latent HSV-1 was recovered compared with the control group. There was no difference between the control group and group I (50 mg/kg/day valacyclovir). However, all three valacyclovir dosages significantly reduced the total number of HSV-1 shedding days compared with the control group, and 100% HSV-1 TG latency was demonstrated for all four groups.[4]

---

The document summarizes clinical trial data and does not provide detailed protocols for animal studies. The reported trials were conducted in immunocompetent human patients. [1]
* **Treatment of First Episode:** A randomized, double-blind study involving 643 patients. Treatment with valacyclovir (1 g twice a day) or acyclovir (200 mg five times a day) was initiated within 72 hours of lesion appearance and continued for 10 days. Intention-to-treat analysis was performed. [1]
* **Treatment of Recurrences:** Patients were enrolled in double-blind trials. Treatment began within 24 hours of the onset of symptoms or recurrence. Various dosing regimens of valacyclovir were compared against acyclovir or placebo for a duration of 5 days. [1]
* **Prevention of Recurrences:** A double-blind, placebo-controlled trial lasting 16 weeks. Patients with at least eight yearly episodes of genital herpes received either valacyclovir (500 mg once daily) or placebo. The primary endpoint was the proportion of patients remaining recurrence-free. [1]

---

The document summarizes clinical trial data and does not provide detailed protocols for animal studies. The reported trials were conducted in immunocompetent human patients. [1]
Treatment of First Episode: A randomized, double-blind study involving 643 patients. Treatment with valacyclovir (1 g twice a day) or acyclovir (200 mg five times a day) was initiated within 72 hours of lesion appearance and continued for 10 days. Intention-to-treat analysis was performed. [1]
Treatment of Recurrences: Patients were enrolled in double-blind trials. Treatment began within 24 hours of the onset of symptoms or recurrence. Various dosing regimens of valacyclovir were compared against acyclovir or placebo for a duration of 5 days. [1]
Prevention of Recurrences: A double-blind, placebo-controlled trial lasting 16 weeks. Patients with at least eight yearly episodes of genital herpes received either valacyclovir (500 mg once daily) or placebo. The primary endpoint was the proportion of patients remaining recurrence-free. [1]

Valacyclovir is a metabolic precursor (prodrug) of acyclovir. It is converted in the body to the active antiviral drug, acyclovir. [1]

Effects During Pregnancy and Lactation
◉ Overview of use during lactation
After valacyclovir administration, the acyclovir content 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 and growth 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.

---

In all reported clinical trials, valacyclovir was well tolerated, with no major differences in the type and frequency of adverse effects compared to acyclovir or placebo. [1]
Adverse effects were generally infrequent and mild. The most frequent adverse events reported were headache (14% to 20% of treated patients), nausea (5% to 6%), and diarrhea (2% to 6%) in one study. In another study, the most frequent adverse effects were headache, nausea, and abdominal pain, each with an incidence below 5%. [1]
Like acyclovir, valacyclovir does not eradicate latent herpes virus. This means that after treatment cessation, the frequency of relapses remains the same as before treatment. [1]

[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.

Valacyclovir hydrochloride is an organic molecular entity. Valacyclovir hydrochloride is an antiviral prescription drug approved by the U.S. Food and Drug Administration (FDA) for: treating and/or preventing certain types of herpes simplex virus (HSV) infection, including genital herpes (genital lesions) and cold sores (cold sores); reducing the risk of transmitting genital herpes to others; and treating varicella-zoster virus (VZV) infection, including chickenpox (primary varicella infection) and shingles (herpesvirus infection). HSV and VZV infections can be opportunistic infections (OIs) of HIV. Opportunistic infections are those that are more common or more severe in people with weakened immune systems (such as those infected with HIV) than in people with healthy immune systems. Valacyclovir hydrochloride is the hydrochloride salt of valacyclovir. Valacyclovir is a prodrug of acyclovir, which, after metabolism, inhibits viral DNA replication. It is used to treat herpes simplex and varicella-zoster virus infections, and can also be used to prevent human cytomegalovirus infection. Valacyclovir is a prodrug of acyclovir, used to treat skin and mucous membrane infections (including genital herpes) caused by herpes zoster and herpes simplex virus. See also: Acyclovir (containing the active fraction); Valacyclovir (containing the active fraction).

---

Valacyclovir (brand name Valtrex®) is an antiviral drug and a metabolic precursor of acyclovir. It is available as 500 mg tablets. [1]
It is licensed for the treatment of initial and recurrent genital herpes simplex virus infections, and for the prevention (suppression) of genital herpes in immunocompetent individuals with at least six recurrences per year. [1]
The primary clinical advantage of valacyclovir over acyclovir is its simplified dosing regimen. It requires only one or two daily doses, compared to five daily doses for acyclovir, which can improve patient compliance. [1]
The recommended dosage for a first episode is 1 g twice daily for 10 days. For recurrences, the recommended dosage is 1 g per day (either as 500 mg twice daily or 1 g once daily) for 5 days. For suppression, the recommended dosage is 500 mg once daily. [1]
The efficacy of valacyclovir in treating genital herpes is relatively limited, similar to acyclovir. It shortens the acute episode by a few days compared to placebo but does not cure the infection. [1]
Patient education on safe sexual practices, such as abstaining from genital contact during acute episodes and using condoms, remains an important part of managing genital herpes. [1]

C13H21CLN6O4

360.799

360.131

C, 43.28; H, 5.87; Cl, 9.83; N, 23.29; O, 17.74

124832-27-5

Valacyclovir-d8 hydrochloride;1279033-32-7;Valacyclovir;124832-26-4;Valacyclovir-d4 hydrochloride;1331910-75-8;Valacyclovir hydrochloride hydrate;1218948-84-5; 124832-27-5 (HCl); 950189-66-9

135398741

Typically exists as white to off-white solids at room temperature

1.55g/cm3

588.4ºC at 760 mmHg

170-172ºC

309.7ºC

7.95E-14mmHg at 25°C

1.673

1.285

4

7

8

24

483

1

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

ZCDDBUOENGJMLV-QRPNPIFTSA-N

InChI=1S/C13H20N6O4.ClH/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);1H/t8-;/m0./s1

2-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]ethyl (2S)-2-amino-3-methylbutanoate;hydrochloride

Zelitrex; 256U87; Vacyclovir; 256U; L-valyl ester; BW256U87; Valacyclovir Hydrochloride; Valtrex L-valylacyclovir; Valacyclovir HCl; Valtrex; Valaciclovir hydrochloride; Valaciclovir Hcl; 256U87 hydrochloride; BW-256U87;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

H2O : ~100 mg/mL (~277.16 mM)
DMSO : ~43.33 mg/mL (~120.09 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.93 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (6.93 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (6.93 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

Solubility in Formulation 4: 100 mg/mL (277.16 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

---

 (Please use freshly prepared in vivo formulations for optimal results.)