HuagongsheHuagongshe Chemistry Print Report · For research reference only
Ganciclovir
GANCYCLOVIR · Vitrasert · GVC · Cytovene · Denosine · GANCICILOVIR · Ganciclovir CRS · 2-AMINO-1,9-[[2-HYDROXY-1-(HYDROXYMETHYL)ETHOXY]METHYL]6H-PURIN-6-ONE(GANCICLOVIR)
Identifiers & Physical Properties
| CAS No. | 82410-32-0 |
|---|---|
| Molecular formula | C9H13N5O4 |
| Average molar mass | 255.23 g/mol |
| Monoisotopic mass | 255.09675391 g/mol |
| SMILES | Nc1nc2c(ncn2COC(CO)CO)c(=O)[nH]1 |
| InChIKey | IRSCQMHQWWYFCW-UHFFFAOYSA-N |
| PubChem CID | 135398740 |
| ChEMBL | CHEMBL182 |
| ChEBI | CHEBI:465284 |
| EC No. | 627-054-3 |
| DTXSID | DTXSID8041032 |
Chemical & Physical Properties
| XLogP | -2.5 |
|---|---|
| Topological polar surface area | 135 |
| Hydrogen bond donors | 4 |
| Hydrogen bond acceptors | 6 |
| Rotatable bonds | 5 |
| Heavy atoms | 18 |
| Formal charge | 0 |
| Complexity | 346 |
| LogP (partition coefficient) | -1.66log Kow = -1.66-1.7 |
| Color/Form | Crystals from methanolWhite to off-white solid |
| Solubility | 4300Ganciclovir sodium sterile powder occurs as a white to off-white, crystalline, lyophilized powder. Ganciclovir sodium has a solubility of 3 mg/mL in water at 25 °C and neutral pH. Both ganciclovir base and ganciclovir sodium are freely soluble in water at high pH (around 11). At more neutral pH, solubility is reduced, and crystallization may occur in concentrated solutions of the drug (exceeding 10 mg/ml). Ganciclovir sodium contains approximately 4 mEq of sodium per gram of ganciclovir. Following reconstitution with sterile water for injection, ganciclovir sodium solutions containing 50 mg of ganciclovir per mL have a pH of approximately 11 and are colorless. Following further dilution in 0.9% sodium chloride injection or 5% dextrose injection, solutions containing approximately 2.5 mg of ganciclovir per mL have a pH of approximately 10 and an osmolality of 310 mOsm/kg. /Ganciclovir sodium/In water (25 °C): 4.3 mg/mL at pH 7Aqueous solubility of the drug is relatively constant over a pH range of 3.5-8.5 but increases substantially in strongly acidic or basic solutions.1.16e+01 g/L>38.3 [ug/mL] (The mean of the results at pH 7.4)0.1 M HCl: 10 mg/mL3.6g/L(25 ºC) |
| Melting point | 250250 °C (decomposes)Crystalline monohydrate from water, MP: 248-249 °C (decomposes)250°C |
| Caco2 Permeability | -6.27 |
| Physical Description | Solid |
| Stability/Shelf Life | Ganciclovir capsules should be stored at 5-25 °C and ganciclovir sodium sterile powder should be stored at room temperatureexposure to temperatures exceeding 40 °C should be avoided. When stored as directed, the sterile powder has an expiration date of 3 years following the date of manufacture.Following reconstitution with sterile water for injection, ganciclovir sodium solutions containing 50 mg of ganciclovir per ml are stable for 12 hr at 15-30 °C and should not be refrigerated since a precipitate may form. ... At a concentration of 10 mg or less of ganciclovir per ml, ganciclovir sodium is physically and chemically stable in the following iv solutions 0.9% sodium chloride, 5% dextrose, Ringer's, or lactated Ringer's. Solutions containing approximately 2.5 mg of ganciclovir per ml reportedly are physically and chemically stable for at least 5 days at 4-25 °C in 0.9% sodium chloride injection or 5% dextrose injection. Although sterility of the solutions was not assessed, results of a recent study indicate that ganciclovir is stable for up to 35 days when diluted in 0.9% sodium chloride or 5% dextrose to a concentration of 1 or 5 mg/ml and stored in polyvinyl chloride containers at 5 °C or 25 °C. In another study, ganciclovir was stable for up to 28 days when diluted in 0.9% sodium chloride or 5% dextrose to a concentration of 5 or 10 mg/ml and stored in polyvinyl chloride containers at 4 °C or -20 °C or stored in ADFuse syringes (Healthtek) at 4 °C. However, /it is/ recommended that diluted (10 mg or less of ganciclovir per ml) solutions of the drug be refrigerated at 2-8 °C and that unused portions of diluted ganciclovir solutions be discarded after 24 hrs since these solutions contain no preservatives. ... Freezing of diluted solutions of the drug is not recommended. Protection of diluted ganciclovir sodium solutions from usual room light is not necessary. The drug does not appear to adsorb appreciably to polyvinyl chloride containers. |
| Dissociation Constants | pKa1 2.2pKa2 9.4 |
| Other Experimental Properties | Crystals from water, MP > 300 °C |
| Boiling point | 398.46°C (rough estimate) |
| Density | 1.3559 (rough estimate) |
| Refractive index | 1.7610 (estimate) |
| Flash point | 9℃ |
| Storage conditions | 2-8°C |
| Physical state | powder |
| pKa (acidity coefficient) | 9.33±0.20(Predicted) |
| Color | white |
| ε(extinction coefficient) | 12.0 at 256nm at 1mM |
| Merck | 14,4363 |
| Henry's law constant | 6.6×1017 mol/(m3Pa) at 25℃, HSDB (2015) |
| InChI | InChI=1S/C9H13N5O4/c10-9-12-7-6(8(17)13-9)11-3-14(7)4-18-5(1-15)2-16/h3,5,15-16H,1-2,4H2,(H3,10,12,13,17) |
| InChIKey | IRSCQMHQWWYFCW-UHFFFAOYSA-N |
| SMILES | N1C2=C(N=C(N)NC2=O)N(COC(CO)CO)C=1 |
| CAS DataBase Reference | 82410-32-0(CAS DataBase Reference) |
| NCI Dictionary of Cancer Terms | ganciclovir |
| FDA UNII | P9G3CKZ4P5 |
| NCI Drug Dictionary | ganciclovir |
| ATC code | J05AB06,S01AD09 |
| Proposition 65 List | Ganciclovir |
| UNSPSC Code | 41116107 |
| NACRES | NA.77 |
| Protein binding | <2% |
| Excreted unchanged in urine | 84.6-94.6% |
| Volume of distribution | 0.54-0.87(L/kg) |
| Biological half-life | 2.9 / 28.5. |
| GHS pictogram | GHS08 |
| Signal word | Danger |
| GHS hazard statements | H340-H361fd |
| GHS precautionary statements | P201-P308+P313 |
| Hazard symbols | T |
| Risk statements (R) | 46-60-61 |
| Safety statements (S) | 53-36/37/39-45 |
| UN transport number | UN1230 - class 3 - PG 2 - Methanol, solution |
| Water hazard class (WGK) | 3 |
| RTECS number | MF8407000 |
| Customs code | 29335990 |
| Storage class | 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects |
| Hazard class | Muta. 1B |
| Hazardous substances data | 82410-32-0(Hazardous Substances Data) |
| Toxicity | LD50 i.p. in mice: 1-2 g/kg (Martin) |
| REACH registrations | Inactive |
Safety & Regulations
| GHS classification | DangerH360 (93.5%): May damage fertility or the unborn child [Danger Reproductive toxicity]P203, P280, P318, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 46 reports by companies from 7 notifications to the ECHA C&L Inventory.Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website. |
|---|---|
| Regulatory information | Hazard Traits - CarcinogenicityDevelopmental ToxicityReproductive ToxicityAuthoritative List - Prop 65Report - regardless of intended function of ingredient in the productStatus: Cease Manufacture Update: 01-06-2016 https://echa.europa.eu/registration-dossier/-/registered-dossier/17541 |
| Fire potential | Not flammable or combustible. |
| FDA requirements | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including ganciclovir, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including ganciclovir sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Ganciclovir sodium/ |
| Hazard Classes and Categories | Repr. 1B (93.5%) |
| Storage conditions | Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature: 2 - 8 °C. Keep in a dry place.Ganciclovir capsules should be stored at 5-25 °C and ganciclovir sodium sterile powder should be stored at room temperatureexposure to temperatures exceeding 40 °C should be avoided. |
| Cleanup methods | Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. Prevent further leakage or spillage if safe to do so. Do not let product enter drains. |
| Interactions | Results of an in vitro study using H9 cells inoculated with HIV (strain HTLV-IIIB) indicate that ganciclovir antagonizes the antiretroviral activity of didanosine against HIV.Results of an in vitro study using H9 cells inoculated with HIV (strain HTLV-IIIB) indicate that ganciclovir antagonizes the antiretroviral activity of zidovudine against HIV. ... Concomitant use of zidovudine with ganciclovir can increase the risk of hematologic toxicity. Both zidovudine and ganciclovir alone produce direct, dose-dependent inhibitory effects on myeloid and erythroid progenitor cells, and combined use of the drugs may result in additive or synergistic myelotoxic effects. In several studies in patients with AIDS and cytomegalovirus infections, profound, intolerable myelosuppression, evidenced principally as severe neutropenia, occurred in all patients receiving zidovudine (200 mg orally every 4 hr) concomitantly with ganciclovir (5 mg/kg iv 1-4 times daily)anemia also occurred in many of these patients. Severe hematologic toxicity, which required a reduction in zidovudine dosage, also occurred in more than 80% of patients receiving zidovudine (100 mg orally every 4 hr) concomitantly with ganciclovir (5 mg/kg iv 1-2 times daily). Several other patients with initially stable hematologic findings on ganciclovir alone, developed prolonged pancytopenia during concomitant therapy with oral zidovudine and iv ganciclovir. The increased risk of hematologic toxicity does not appear to be related to a pharmacokinetic interaction between ganciclovir and zidovudine since there is no evidence that concomitant use affects the pharrnacokinetic parameters of either drug.Foscarnet has exhibited additive or synergistic antiviral activity with ganciclovir in vitro and/or in vivo against cytomegalovirus and herpes simplex virus type 2. In addition, combined therapy with the drugs may be effective in the treatment of cytomegalovirus infection resistant to either drug alone.Although renal excretion of ganciclovir appears to occur principally via glomerular filtration, limited renal secretion of the drug also may occur. Therefore, ... the possibility that probenecid or other drugs that inhibit renal tubular secretion or reabsorption may interfere with the renal clearance and urinary excretion of ganciclovir should be considered.For more Interactions (Complete) data for GANCICLOVIR (10 total), please visit the HSDB record page. |
| Environmental fate | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that ganciclovir is expected to have very high mobility in soil(SRC). Volatilization of ganciclovir from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.5X10-23 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Ganciclovir is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.5X10-17 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Biodegradation data in soil were not available(SRC, 2013).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that ganciclovir is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.5X10-23 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow of -1.66(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Ganciclovir is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Biodegradation data in water were not available(SRC, 2013).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ganciclovir, which has an estimated vapor pressure of 4.5X10-17 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase ganciclovir may be removed from the air by wet or dry deposition(SRC). Ganciclovir contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). |
| Milk Concentrations | /Ganciclovir/ appears to distribute into milk in animals. |
| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc of ganciclovir can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that ganciclovir is expected to have very high mobility in soil. |
| Human Toxicity Excerpts | /HUMAN EXPOSURE STUDIES/ In placebo controlled studies in transplant recipients, sepsis occurred in 6% of patients receiving ganciclovir and 2% of patients receiving placebo./HUMAN EXPOSURE STUDIES/ This study aimed to evaluate the effectiveness of ganciclovir (GCV) treatment for severe cytomegalovirus (CMV)-associated pneumonia in immunocompetent children. /The authors/ enrolled patients with CMV-associated severe pneumonia admitted to the Vietnam National Hospital of Pediatrics, Hanoi, Vietnam, from January 2010 to December 2011. On admission, though respiratory bacteria and viruses were not detected in tracheal aspirates, more than 5 x 103 copies/mL of CMV-DNA were detected in both tracheal aspirates and in blood plasma. GCV was given intravenously at a dose of 10 mg/kg/24 hr for a duration of 14 days at most. The dose was then reduced to 5 mg/kg/24 hr until CMV-DNA was not detected in plasma. The main study variables included clinical symptoms, complete blood count, hepatic and renal function, chest X-ray, CMV viral load, duration of GCV treatment and outcome. Forty-three patients were enrolled in the study. The median age of patients was 57 (interquartile range (IQR) 45--85) days. Clinical and laboratory findings included anemia (67.4%), leukocytosis (90.7%), hepatosplenomegaly (60.5%), elevated liver enzymes (74.4%), decreased ratio of CD4:CD8-positive T lymphocytes (69.4%), and decreased serum IgG concentration (25.7%). The median duration of GCV treatment was 12 days (IQR 7-21). Thirty-seven patients (86.0%) showed normal chest X-rays at the end of treatment. One infant died (2.3%)the other children (97.7%) were discharged in good condition. There was no severe toxicity associated with GCV treatment. GCV is safe and effective for the treatment of severe CMV-associated pneumonia in children./SIGNS AND SYMPTOMS/ Neutropenia (absolute neutrophil count less than 1000/cu mm), which is potentially fatal, occurs in up to 25-50% of patients receiving ganciclovir and is the most common dose limiting adverse effect of the drug. The absolute neutrophil count declines to less than 500/cu mm in approximately 15-20% of patients receiving the drug for the treatment of cytomegalovirus infection. Neutropenia usually develops early in treatment (eg, during the first or seeond week of induetion therapy), but can occur at any time. ... Thrombocytopenia (platelet count less than 50,000/cu mm) also occurs frequently in patients receiving ganciclovir, developing in approximately 20% of patients who receive the drug for treatment of cytomegalovirus infection. Approximately 10% of patients develop platelet counts less than 20,000/cu mm. Interruption of ganciclovir therapy or a decrease in dosage usually results in increased platelet counts. Patients with low baseline platelet counts (less than 100,000/cu mm) appear to be more prone to develop this reaction. In addition, patients who are iatrogenically immunosuppressed appear to be at greater risk than AIDS patients of developing thrombocytopenia, which occurred in 46 and 14% of such patients, respectively, in one study. ... Less frequent adverse hematologic effects of ganciclovir include anemia and eosinophilia, occurring inapproximately 2% and less than 1% of patients, respectively, receiving the drug./SIGNS AND SYMPTOMS/ Rhegmatogenous retinal detachment can develop as a consequence of ganciclovir induced resolution of retinitis. Such detachment is thought to result from the hastening of the involutional stage of the disease in which the retina thins as necrotic tissue is mobilized and edema fluid resorbsthese changes predispose the retina to tears and detachment. Retinal detachment has been reported in up to 30% of ganciclovir treated patients with cytomegalovirus retinitis. ... This complication appears to occur more frequently in AIDS patients than in other immunosuppressed patients and may be related to the inability of AIDS patients to form firm scar tissue, secondary to impaired inflammatory responses, as the retina heals.For more Human Toxicity Excerpts (Complete) data for GANCICLOVIR (24 total), please visit the HSDB record page. |
| Artificial Pollution Sources | Ganciclovir's production and administration as an antiviral(1) may result in its release to the environment through various waste streams(SRC). |
| Drug Induced Liver Injury | Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)ganciclovirCytovene®Antivirals7less-DILI-concern drugs |
| Environmental Bioconcentration | An estimated BCF of 3 was calculated in fish for ganciclovir(SRC), using a log Kow of -1.66(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC). |
| Volatilization from Water/Soil | The Henry's Law constant for ganciclovir is estimated as 1.5X10-23 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that ganciclovir is expected to be essentially nonvolatile from moist soil and water surfaces(2). Ganciclovir is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.9X10-17 mm Hg(SRC), determined from a fragment constant method(3). |
| Non-Human Toxicity Excerpts | /LABORATORY ANIMALS: Acute Exposure/ In acute toxicity studies in mice and dogs, the median acute iv dose of ganciclovir was 900 and 150-500 mg/kg, respectively. Death was associated with bone marrow suppression and renal dysfunction along with gastric (mucosal discoloration and evidence of sanguinous material) and intestinal (distention and reddening) pathologic changes. Toxic manifestations of a single 500 mg/kg iv dose in these animals included emesis, hypersalivation, anorexia, bloody diarrhea, inactivity, cytopenias, elevated liver function test results, testicular atrophy, elevated blood urea nitrogen, and obstructive nephropathy./LABORATORY ANIMALS: Acute Exposure/ There was no evidence of vascular irritation following injection of ganciclovir into the marginal ear veins of rabbits. ... Intravitreal injection of the drug in a limited number of animals ... did not appear to produce oculotoxic effects, although other local ocular effects occasionally were observed./LABORATORY ANIMALS: Acute Exposure/ In a study in rabbits, intravitreal injection of single ganciclovir doses ranging from 10-400 ug at concentrations of 1-20 ug/mL produced no discernible ophthalmologic or histologic changes in the eye or in electroretinographic B waves./LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ An 18 month study in mice given oral ganciclovir dosages of 1 g/kg daily revealed an increased incidence of tumors in the preputial gland of males, in the nonglandular gastric mucosa of males and females, and in the reproductive tissues and liver of females. At an oral dosage of 20 mg/kg daily in this study, there was a slightly increased incidence of tumors in the preputial and harderian glands of males, in the nonglandular gastric mucosa of both males and females, and in the liver of females. All ganciclovir induced tumors were of epithelial or vascular origin, except for histocytic sarcoma of the liver. No carcinogenic effects were observed at an oral dosage of 1 mg/kg daily. Although the relevance of these findings to humans is not known since the nonglandular stomach and preputial, clitoral, and harderian glands have no human counterparts, ... ganciclovir still should be considered a potential carcinogen in humans.For more Non-Human Toxicity Excerpts (Complete) data for GANCICLOVIR (13 total), please visit the HSDB record page. |
| Environmental Abiotic Degradation | Ganciclovir is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Ganciclovir contains chromophores that absorb at wavelengths >290 nm(1) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). |
| Probable Routes of Human Exposure | Occupational exposure to ganciclovir may occur through inhalation and dermal contact with this compound at workplaces where ganciclovir is produced or used. Use data indicate that the general population may be exposed to ganciclovir via medical administration of this compound for the treatment of viral infection. (SRC) |
| Water hazard class (WGK) | 3 |
| RTECS number | MF8407000 |
| UN transport number | UN1230 - class 3 - PG 2 - Methanol, solution |
| Customs code | 29335990 |
| Toxicity | LD50 i.p. in mice: 1-2 g/kg (Martin) |
| Risk statements (R) | 46-60-61 |
| Signal word | Danger |
| GHS pictogram | GHS08 |
| Hazard symbols | T |
| Safety statements (S) | 53-36/37/39-45 |
| Storage class | 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects |
| GHS hazard statements | H340-H361fd |
| REACH registrations | Inactive |
| Hazard class | Muta. 1B |
| GHS precautionary statements | P201-P308+P313 |
| Hazardous substances data | 82410-32-0(Hazardous Substances Data) |
Applications & Uses
Description
Ganciclovir is a synthetic analog of 2''-deoxy-guanosine which is used to treat or prevent cytomegalovirus (CMV) infections. It inhibits the replication of human CMV with an IC50 value of 0.01 μM and is effective against strains of CMV from human, monkey, mouse, and guinea pig.
Description
Ganciclovir is a parenterally-active antiviral agent indicated for sight- or life-threatening cytomegalovirus (CMV) infections in immunocompromised patients. Its suppressive effects on bone marrow and renal tubular secretion/absorption are reported to present potential limitations on adjunct therapies involving zidovudine, vincristine, adriamycin and amphotericin B. Recently, the emergence of CMV strains resistant to ganciclovir therapy has been reported.
Uses
antiemetic
Uses
Ganciclovir is a nucleoside analog structurally related to Acyclovir (A192400). Ganciclovir is an antiviral.
Uses
Ganciclovir may be used as a pharmaceutical reference standard for the determination of the analyte in pharmaceutical formulations by chromatography techniques.
General Description
Ganciclovir, 9-[(1,3-dihydroxy-2-propoxy) methyl]guanine)or DHPG (Cytovene), is an analog of acyclovir, with an additional hydroxymethyl group on the acyclic side chain.After administration, similar to acyclovir, ganciclovir isphosphorylated inside the cell by a virally encoded proteinkinase to the monophosphate.Host cell enzymes catalyzethe formation of the triphosphate, which reaches more than10-fold higher concentrations in infected cells than in uninfectedcells. The clinical usefulness of ganciclovir is limited by thetoxicity of the drug. Ganciclovir causes myelosuppression,producing neutropenia, thrombocytopenia, and anemia.These effects are probably associated with inhibition of hostcell DNA polymerase.Potential central nervous systemside effects include headaches, behavioral changes, and convulsions.Ganciclovir is mutagenic, carcinogenic, and teratogenicin animals.