Absorption, Distribution and Excretion
Valganciclovir tablets are well absorbed from the gastrointestinal tract, with an absolute bioavailability of approximately 60% when taken with food. Valganciclovir is primarily excreted by the kidneys as ganciclovir via glomerular filtration and active tubular secretion.
0.703 ± 0.134 L/kg
3.07 ± 0.64 mL/min/kg [intravenous administration]
5.3 L/hr [patients with a creatinine clearance of 70.4 mL/min]
Valganciclovir is primarily excreted by the kidneys as ganciclovir via glomerular filtration and active tubular secretion. The plasma concentration of ganciclovir after intravenous injection was 3.07 ± 0.64 mL/min/kg (n=68), and the renal clearance was 2.99 ± 0.67 mL/min/kg (n=16), i.e., systemic clearance. Because valganciclovir is rapidly converted to ganciclovir, plasma protein binding of valganciclovir was not determined. Plasma protein binding of ganciclovir ranged from 1% to 2% at concentrations of 0.5 and 51 μg/mL. The steady-state volume of distribution after intravenous administration of ganciclovir was 0.703 ± 0.134 L/kg (n=69). No correlation was observed between ganciclovir AUC and the reciprocal of body weight after administration of valganciclovir tablets. Oral administration of Valcyte tablets based on body weight is not required. When 16 HIV-positive subjects took 875 mg Valcyte tablets once daily, along with a high-fat meal of approximately 600 calories (31.1 g fat, 51.6 g carbohydrates, and 22.2 g protein), the steady-state AUC of ganciclovir increased by 30% (95% CI 12% to 51%), and Cmax increased by 14% (95% CI -5% to 36%), but the time to peak concentration (Tmax) was not prolonged. Valcyte should be taken with food. The bioavailability of ganciclovir after oral administration was approximately ten times that after oral administration (60% vs. 5.6%, respectively). Adult pharmacokinetic studies showed that the area under the plasma concentration-time curve (AUC0–24 hours) of once-daily oral administration of 900 mg ganciclovir (with food) was comparable to that of once-daily intravenous administration of 5 mg/kg ganciclovir and higher than that of three-times oral administration of 1 g ganciclovir (with food). However, at these doses, oral valganciclovir showed lower peak plasma concentrations and lower trough plasma concentrations than intravenously administered valganciclovir. Differences (if any) in peak and trough plasma drug concentrations among these three ganciclovir delivery systems have not been determined, and their clinical significance is unclear. For more complete data on absorption, distribution, and excretion of valganciclovir (7 in total), please visit the HSDB record page. Metabolites/Metabolites: Rapidly hydrolyzed to ganciclovir in the intestinal wall and liver. No other metabolites were detected. It is an L-valine ester (prodrug) of ganciclovir, existing as a mixture of two diastereomers. After oral administration, both diastereomers are rapidly converted to ganciclovir by intestinal and hepatic esterases. … Rapidly hydrolyzed to ganciclovir; no other metabolites were detected. Following oral administration of radiolabeled ganciclovir (single dose 1000 mg), radioactive material recovered in feces or urine accounts for more than 1% to 2% of the total radioactivity. No metabolites are produced. The biological half-life is approximately 4.08 hours. The half-life is prolonged in patients with impaired renal function. ...Ten patients were evaluated. The mean age was 56.8 ± 3.4 years, and the mean creatinine clearance was 69 ± 9 mL/min. After administration of valganciclovir, the oral bioavailability of ganciclovir was 59%, and the mean half-life was 3.73 ± 1.15 hours. ... In healthy subjects or HIV-positive/CMV-positive subjects, the terminal half-life of ganciclovir after oral administration of Valcyte tablets was 4.08 ± 0.76 hours (n=73), and the terminal half-life after intravenous administration of ganciclovir was 3.81 ± 0.71 hours (n=69). In patients undergoing heart, kidney, combined kidney-pancreas transplantation, and liver transplantation, the terminal elimination half-life of ganciclovir after oral Valcyte was 6.48 ± 1.38 hours, and the terminal elimination half-life after oral ganciclovir capsules was 8.56 ± 3.62 hours.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
It can rapidly convert to ganciclovir (valganciclovir). This may influence a breastfeeding woman's decision to use valganciclovir. Multiple factors. There is currently no clinical information regarding the use of ganciclovir or valganciclovir during breastfeeding. It can be transmitted to the infant through breast milk, with preterm and immunocompromised infants at the highest risk. Cytomegalovirus (CMV). There is currently no information regarding changes in the risk of transmission when the mother is treated with ganciclovir or valganciclovir. Although the manufacturer recommends avoiding breastfeeding while taking valganciclovir due to the risk of drug toxicity in the infant, newborns infected with CMV are usually treated directly with ganciclovir or valganciclovir. Breastfeeding is not recommended in the United States and other developed countries if the mother is also infected with HIV.
◉ Effects on Breastfed Infants
As of the revision date, no published information was found.
◉ Effects on lactation and breast milk
No published information was found as of the revision date.

---

Protein binding
The plasma protein binding of ganciclovir was 1% to 2% at concentrations of 0.5 and 51 mg/mL.

---

Interactions
Potential pharmacological interactions (hematologic toxicity superposition (neutropenia, anemia)) / Concomitant use with valganciclovir and zidovudine.
Potential pharmacokinetic interactions / Concomitant use with valganciclovir and probenecid / (decreased renal clearance and increased AUC).
Ganciclovir); monitor ganciclovir toxicity.
Potential drug interactions (hematologic toxicity superposition) / Concomitant use with valganciclovir and myelosuppressants or radiotherapy /.
Potential pharmacokinetic interactions / Concomitant use with valganciclovir and mycophenolate mofetil / In patients with renal impairment (elevated plasma concentrations of both drug metabolites). For more complete data on valganciclovir interactions (6 items in total), please visit the HSDB record page.

[1]. Transport of valganciclovir, a ganciclovir prodrug, via peptide transporters PEPT1 and PEPT2. J Pharm Sci. 2000 Jun;89(6):781-9.

[2]. Oral valganciclovir versus ganciclovir as delayed pre-emptive therapy for patients after allogeneic hematopoietic stem cell transplant: a pilot trial (04-0274) and review of the literature. Transpl Infect Dis. 2012 Jun;14(3):259-67.

[3]. Valganciclovir prevents cytomegalovirus reactivation in patients receiving alemtuzumab-based therapy. Blood. 2008 Feb 15;111(4):1816-9.

Therapeutic Uses
Antiviral Drug
For the treatment of cytomegalovirus (CMV) retinitis in adults (including those with acquired immunodeficiency syndrome (AIDS)) as initial (induction) and maintenance therapy (secondary prevention). Valganciclovir Hydrochloride Tablets. /Included on US Product Label/
Oral valganciclovir is also recommended for the treatment and secondary prevention of CMV retinitis in older children and adolescents with HIV infection who can receive adult doses. Recommended by the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the Infectious Diseases Society of America (IDSA). /Not Included on US Product Label/
For the prevention of cytomegalovirus (CMV) infection in adult recipients of kidney, heart, and kidney-pancreas combined transplants (CMV seronegative recipients receiving organs from CMV seropositive donors). Valganciclovir Hydrochloride Tablets. /Included on US Product Label/
Cytomegalovirus (CMV) is the most common viral infection following solid organ transplantation (SOT). Reducing the rate of CMV infection after SOT is crucial for long-term transplant survival. Safe and effective prevention is essential. Although valganciclovir has not yet been approved by the U.S. Food and Drug Administration (FDA) for CMV prophylaxis in liver transplant recipients, post-marketing studies have shown that valganciclovir is as effective as ganciclovir in high-risk adult patients undergoing standard organ transplantation (SOT). Currently, data on pediatric liver transplantation are lacking. This study aimed to compare the efficacy and safety of valganciclovir and ganciclovir in the prevention of cytomegalovirus (CMV) infection in pediatric liver transplant recipients. This was a retrospective study that included 56 pediatric liver transplant recipients, who received either oral ganciclovir (n=37) or valganciclovir (n=19). All patients were followed up until 200 days post-transplantation or death. The study compared the incidence of early CMV infection and CMV disease in the two groups. The primary endpoint was to identify patient-specific factors contributing to CMV infection and late CMV infection or disease. Secondary endpoints included adverse events and discontinuation rates. Adverse events and discontinuation rates were 0% in the valganciclovir group and 5.4% in the ganciclovir group (P=0.54). No statistically significant differences were observed in secondary endpoints. An increased incidence of delayed-type cytomegalovirus (CMV) disease was observed in the valganciclovir group (22.2% vs. 8.1%, P = 0.23) compared to the ganciclovir group. No differences in adverse events were reported. In conclusion, there was no statistically significant difference in the incidence of CMV infection or disease between the oral valganciclovir group and the oral ganciclovir group.

---

Drug Warning
/Black Box Warning/ Warning: Hematologic toxicity, carcinogenicity, teratogenicity, and reproductive toxicity. Valganciclovir is metabolized to ganciclovir, whose clinical toxicities include granulocytopenia, anemia, and thrombocytopenia. Animal studies have shown that ganciclovir is carcinogenic, teratogenic, and can cause azoospermia. Valganciclovir is metabolized to ganciclovir, and its toxicities include granulocytopenia, anemia, and thrombocytopenia. Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, myeloablation, and aplastic anemia have been reported in patients treated with valganciclovir or ganciclovir. These adverse reactions can occur at any time, and the degree of cytopenia may worsen with continued valganciclovir treatment. Cytopenia usually begins to return to baseline levels 3–7 days after discontinuation of the drug. Frequent blood cell counts should be performed, especially in patients with a baseline neutrophil count below 1000/mm³ and in patients who develop leukopenia while receiving ganciclovir or other nucleoside analogues. Complete blood counts (CBCs) and platelet counts should be performed. Blood cell counts may be necessary if the treatment regimen is changed from oral ganciclovir to valganciclovir (because valganciclovir can relatively increase plasma ganciclovir concentrations). More frequent monitoring for cytopenia is necessary. Valganciclovir should not be used in patients with an absolute neutrophil count below 500/mm³, a platelet count below 25,000/mm³, or a hemoglobin concentration below 8 g/dL. Caution should be exercised when using valganciclovir in patients with a history of cytopenia, or those who have received or are receiving myelosuppressive drugs or radiation therapy. Valganciclovir is considered carcinogenic, mutagenic, teratogenic, and may cause spermatogenesis disorders. Animal data show that valganciclovir can be converted to ganciclovir, and its carcinogenicity and reproductive toxicity are expected to be similar to ganciclovir. Valganciclovir is considered a potential human carcinogen and may have teratogenic or embryotoxic effects at commonly used therapeutic doses. Valganciclovir may temporarily or permanently inhibit spermatogenesis and may suppress female fertility. Women of reproductive age are advised to use effective contraception during and for at least 30 days after valganciclovir treatment. Male patients are advised to use reliable barrier contraception during and for at least 90 days after treatment with valganciclovir. Acute renal failure may occur in elderly patients (with or without renal impairment), patients taking potentially nephrotoxic drugs, and dehydrated patients. All patients should maintain adequate hydration. Caution should be exercised when using this medication, and the dosage of valganciclovir should be adjusted according to creatinine clearance. Caution should be exercised when using this medication in patients taking potentially nephrotoxic drugs. For more complete data on drug warnings (of 16) for valganciclovir, please visit the HSDB record page.

---

Pharmacodynamics
Valganciclovir is an antiviral drug used to treat cytomegalovirus infection. As an L-valine ester of ganciclovir, it is actually a prodrug of ganciclovir. After oral administration, it is rapidly converted to ganciclovir by esterases in the intestine and liver. Ganciclovir (as a guanosine analogue) is then incorporated into DNA, preventing proper reading by DNA polymerases, ultimately leading to termination of viral DNA elongation.

C14H22N6O5

354.36168

354.165

175865-60-8

Valganciclovir hydrochloride;175865-59-5;Valganciclovir-d5 TFA;1402924-31-5

135413535

Typically exists as solid at room temperature

1.6±0.1 g/cm3

629.1±65.0 °C at 760 mmHg

334.3±34.3 °C

0.0±1.9 mmHg at 25°C

1.678

-1.28

4

8

9

25

528

1

N[C@@H](C(C)C)C(OCC(OCN1C=NC2=C1N=C(N)NC2=O)CO)=O

WPVFJKSGQUFQAP-GKAPJAKFSA-N

InChI=1S/C14H22N6O5/c1-7(2)9(15)13(23)24-4-8(3-21)25-6-20-5-17-10-11(20)18-14(16)19-12(10)22/h5,7-9,21H,3-4,6,15H2,1-2H3,(H3,16,18,19,22)/t8?,9-/m0/s1

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

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

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

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