DT-Web

DB01610 - Valganciclovir


Identification
Name Valganciclovir
Accession Number DB01610
Type small molecule
Description Valganciclovir hydrochloride (Valcyte, manufactured by Roche) is an antiviral medication used to treat cytomegalovirus infections. As the L-valyl ester of ganciclovir, it is actually a prodrug for ganciclovir. After oral administration, it is rapidly converted to ganciclovir by intestinal and hepatic esterases.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 354.3617
Groups approved
Monoisotopic Weight 354.165167844
Pharmacology
Indication Valganciclovir is an antiviral medication used for the treatment of cytomegalovirus infections.
Mechanism of action Valganciclovir is a prodrug of ganciclovir that exists as a mixture of two diastereomers. After administration, these diastereomers are rapidly converted to ganciclovir by hepatic and intestinal esterases. In cytomegalovirus (CMV)-infected cells, ganciclovir is initially phosphorylated to the monophosphate form by viral protein kinase, then it is further phosphorylated via cellular kinases to produce the triphosphate form. This triphosphate form is slowly metabolized intracellularly. The phosphorylation is dependent upon the viral kinase and occurs preferentially in virus-infected cells. The virustatic activity of ganciclovir is due to the inhibition of viral DNA synthesis by ganciclovir triphosphate. Ganciclovir triphosphate is incorporated into the DNA strand replacing many of the adenosine bases. This results in the prevention of DNA synthesis, as phosphodiester bridges can longer to be built, destabilizing the strand. Ganciclovir inhibits viral DNA polymerases more effectively than it does cellular polymerase, and chain elongation resumes when ganciclovir is removed.
Absorption Valganciclovir is well absorbed from the gastrointestinal tract and the absolute bioavailability from valganciclovir tablets (following administration with food) is approximately 60%.
Protein binding Plasma protein binding of ganciclovir is 1% to 2% over concentrations of 0.5 and 51 mg/mL.
Biotransformation Rapidly hydrolyzed in the intestinal wall and liver to ganciclovir. No other metabolites have been detected.
Route of elimination The major route of elimination of valganciclovir is by renal excretion as ganciclovir through glomerular filtration and active tubular secretion.
Toxicity It is expected that an overdose of valganciclovir could also possibly result in increased renal toxicity.
Affected organisms
  • Human Herpes Virus
Interactions
Drug Interactions
Drug Mechanism of interaction
Abacavir The adverse/toxic effects of reverse transcriptase inhibitors (nucleoside), such as Abacavir, may be enhanced by Valganciclovir. There is a risk of hematologic toxicity. Diligent monitoring during concomitant therapy is recommended.
Adefovir Dipivoxil The adverse/toxic effects of reverse transcriptase inhibitors (nucleoside), such as Adefovir Dipivoxil, may be enhanced by Valganciclovir. There is a risk of hematologic toxicity. Diligent monitoring during concomitant therapy is recommended.
Cilastatin Generalized convulsions have been reported in patients taking Ganciclovir and Imipenem-cilastatin. Concomitant therapy should be avoided. (Note: Valganciclovir is converted to Ganciclovir in vivo)
Didanosine The adverse/toxic effects of Didanosine, a reverse transcriptase inhibitor (nucleoside), may be enhanced by Valganciclovir. There is a significant risk of hematologic toxicity. Concomitant therapy should be avoided.
Emtricitabine The adverse/toxic effects of reverse transcriptase inhibitors (nucleoside), such as Emtricitabine, may be enhanced by Valganciclovir. There is a risk of hematologic toxicity. Diligent monitoring during concomitant therapy is recommended.
Imipenem Generalized convulsions have been reported in patients taking Ganciclovir and Imipenem-cilastatin. Concomitant therapy should be avoided. (Note: Valganciclovir is converted to Ganciclovir in vivo)
Lamivudine The adverse/toxic effects of reverse transcriptase inhibitors (nucleoside), such as Lamivudine, may be enhanced by Valganciclovir. There is a risk of hematologic toxicity. Diligent monitoring during concomitant therapy is recommended.
Mycophenolate mofetil The excretion rates of Valganciclovir and/or Mycophenolate mofetil may decrease. Monitor for increased serum concentrations and toxicity of both agents.
Mycophenolic acid The excretion rates of Valganciclovir and/or Mycophenolic acid may decrease. Monitor for increased serum concentrations and toxicity of both agents.
Probenecid Probenecid may decrease excretion of Valganciclovir. Monitor for increased serum concentration and toxicity of Valganciclovir.
Tenofovir The excretion rates of Valganciclovir and/or Tenofovir may decrease as both drugs are eliminated by active tubular secretion. Monitor for increased serum concentrations and toxicity of both agents.
Zidovudine The adverse/toxic effects of Zidovudine, a reverse transcriptase inhibitor (nucleoside), may be enhanced by Valganciclovir. There is a significant risk of hematologic toxicity. Concomitant therapy should be avoided.
Food Interactions Not Available

Targets


DNA
Name DNA
Gene Name Not Available
Pharmacological action yes
Actions adduct
References
  • Martin M, Azzi A, Lin SX, Boivin G: Opposite effect of two cytomegalovirus DNA polymerase mutations on replicative capacity and polymerase activity. Antivir Ther. 2010;15(4):579-86. - Pubmed
  • Boivin G, Goyette N, Gilbert C, Covington E: Analysis of cytomegalovirus DNA polymerase (UL54) mutations in solid organ transplant patients receiving valganciclovir or ganciclovir prophylaxis. J Med Virol. 2005 Nov;77(3):425-9. - Pubmed
  • Marfori JE, Exner MM, Marousek GI, Chou S, Drew WL: Development of new cytomegalovirus UL97 and DNA polymerase mutations conferring drug resistance after valganciclovir therapy in allogeneic stem cell recipients. J Clin Virol. 2007 Feb;38(2):120-5. Epub 2006 Dec 8. - Pubmed
  • Potena L, Holweg CT, Chin C, Luikart H, Weisshaar D, Narasimhan B, Fearon WF, Lewis DB, Cooke JP, Mocarski ES, Valantine HA: Acute rejection and cardiac allograft vascular disease is reduced by suppression of subclinical cytomegalovirus infection. Transplantation. 2006 Aug 15;82(3):398-405. - Pubmed
DTHybrid score Not Available

Transporters


Oligopeptide transporter, small intestine isoform
Name Oligopeptide transporter, small intestine isoform
Gene Name SLC15A1
Actions Not Available
References
  • Sugawara M, Huang W, Fei YJ, Leibach FH, Ganapathy V, Ganapathy ME: Transport of valganciclovir, a ganciclovir prodrug, via peptide transporters PEPT1 and PEPT2. J Pharm Sci. 2000 Jun;89(6):781-9. - Pubmed
DTHybrid score 0.5613
Oligopeptide transporter, kidney isoform
Name Oligopeptide transporter, kidney isoform
Gene Name SLC15A2
Actions Not Available
References
  • Sugawara M, Huang W, Fei YJ, Leibach FH, Ganapathy V, Ganapathy ME: Transport of valganciclovir, a ganciclovir prodrug, via peptide transporters PEPT1 and PEPT2. J Pharm Sci. 2000 Jun;89(6):781-9. - Pubmed
DTHybrid score 0.5527
Sodium- and chloride-dependent neutral and basic amino acid transporter B(0+)
Name Sodium- and chloride-dependent neutral and basic amino acid transporter B(0+)
Gene Name SLC6A14
Actions Not Available
References
  • Umapathy NS, Ganapathy V, Ganapathy ME: Transport of amino acid esters and the amino-acid-based prodrug valganciclovir by the amino acid transporter ATB(0,+). Pharm Res. 2004 Jul;21(7):1303-10. - Pubmed
DTHybrid score 0.321

Predictions


Id Partner name Gene Name Score
244 Angiotensin-converting enzyme ACE 0.1747
633 Penicillin-binding proteins 1A/1B pbpA 0.1007
1729 Solute carrier family 22 member 6 SLC22A6 0.0884
5469 Head decoration protein shp 0.0863
118 Organic cation/carnitine transporter 2 SLC22A5 0.0813
6142 Solute carrier family 22 member 8 SLC22A8 0.0561
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0516
6151 Monocarboxylate transporter 10 SLC16A10 0.0513
509 Thymidine kinase TK 0.0506
570 Thymidine kinase TK 0.0506
2559 Thymidine kinase TK 0.0506
3430 Thymidine kinase tdk 0.0506
3518 Thymidine kinase TK 0.0506
5301 Thymidine kinase tdk 0.0506
5771 Thymidine kinase ORF36 0.0506
7009 Thymidine kinase ORF36 0.0506
482 Glycine receptor subunit alpha-1 GLRA1 0.0459
1 Peptidoglycan synthetase ftsI ftsI 0.0442
4155 Peptidoglycan synthetase ftsI ftsI 0.0442
338 DNA polymerase UL30 0.0432
379 DNA polymerase UL54 0.0432
697 DNA polymerase ORF28 0.0432
2482 DNA polymerase 43 0.0432
4104 DNA polymerase BALF5 0.0432
645 Penicillin-binding protein 1A mrcA 0.0413
5805 Penicillin-binding protein 1A ponA 0.0413
6185 Penicillin-binding protein 1A mrcA 0.0413
6799 Penicillin-binding protein 1A pbpA 0.0413
6140 Ileal sodium/bile acid cotransporter SLC10A2 0.0407
1385 Angiotensin-converting enzyme 2 ACE2 0.035
587 Serum albumin ALB 0.0315
543 Penicillin-binding protein 1B mrcB 0.0309
6186 Penicillin-binding protein 1B ponB 0.0309
6822 Penicillin-binding protein 1b pbp1b 0.0309
6844 Penicillin-binding protein 1b pbp1b 0.0309
1588 Multidrug resistance protein 1 ABCB1 0.028
234 Plasminogen PLG 0.0246
1757 Myeloperoxidase MPO 0.0242
115 Penicillin-binding protein 2 mrdA 0.0235
6069 Penicillin-binding protein 2 mrdA 0.0235
6118 Penicillin-binding protein 2 penA 0.0235
6187 Penicillin-binding protein 2 pbpA 0.0235
6686 Penicillin-binding protein 2 pbp2 0.0235
6939 Penicillin-binding protein 2 mrdA 0.0235
7163 Penicillin-binding protein 2 pbpA 0.0235
6067 Penicillin binding protein 2a mecA 0.0233
56 Delta-aminolevulinic acid dehydratase ALAD 0.023
2356 Delta-aminolevulinic acid dehydratase hemB 0.023
3613 Delta-aminolevulinic acid dehydratase hemB 0.023
3674 Delta-aminolevulinic acid dehydratase hemB 0.023
3923 Cholinesterase BCHE 0.0203
230 ATP-binding cassette transporter sub-family C member 8 ABCC8 0.0203
2544 Bacterial leucyl aminopeptidase Not Available 0.0198
1024 Solute carrier family 22 member 11 SLC22A11 0.0197
797 Sodium-dependent proline transporter SLC6A7 0.0191
4083 Peptidyl-prolyl cis-trans isomerase H PPIH 0.019
4085 Peptidyl-prolyl cis-trans isomerase C PPIC 0.019
4087 Pyrroline 5-carboxylate reductase isoform P5CR2 0.0189
4082 Proline oxidase, mitochondrial PRODH 0.0189
4090 Chromosome 14 open reading frame 149 C14orf149 0.0189
4088 Probable prolyl-tRNA synthetase, mitochondrial PARS2 0.0189
4086 Peptidyl-prolyl cis-trans isomerase G PPIG 0.0189
4512 Cytochrome P450 3A4 CYP3A4 0.0178
4604 Liver carboxylesterase 1 CES1 0.0175
6016 Cytochrome P450 2C19 CYP2C19 0.0172
3917 Methylenetetrahydrofolate reductase MTHFR 0.0164
4084 Peptidyl-prolyl cis-trans isomerase B PPIB 0.0161
4000 Prolyl 4-hydroxylase subunit alpha-2 P4HA2 0.0157
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0155
248 Pyrroline-5-carboxylate reductase 1 PYCR1 0.0153
802 Pyrroline-5-carboxylate reductase 2 PYCR2 0.0153
3874 Proline synthetase co-transcribed bacterial homolog protein PROSC 0.015
3060 Leukotriene A-4 hydrolase LTA4H 0.0149
2554 Peptidyl-prolyl cis-trans isomerase, mitochondrial PPIF 0.0147
210 Bifunctional aminoacyl-tRNA synthetase [Includes: Glutamyl-tRNA synthetase EPRS 0.014
3949 Prolyl 3-hydroxylase 2 LEPREL1 0.0139
3945 Prolyl 3-hydroxylase 1 LEPRE1 0.0139
3951 Prolyl 3-hydroxylase 3 LEPREL2 0.0139
6143 Solute carrier family 22 member 7 SLC22A7 0.0135
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.013
1524 Peptidyl-prolyl cis-trans isomerase A PPIA 0.013
6700 Peptidyl-prolyl cis-trans isomerase A ppiA 0.013
67 Prolyl 4-hydroxylase subunit alpha-1 P4HA1 0.0128
4119 Cytochrome P450 2D6 CYP2D6 0.0127
159 Penicillin-binding protein 2B penA 0.0123
6121 Penicillin-binding protein 2B penA 0.0123
4252 Penicillin-binding protein 5 dacA 0.0117
4757 Cytochrome P450 2C9 CYP2C9 0.0117
738 Monocarboxylate transporter 1 SLC16A1 0.0104
332 Beta-lactamase blaZ 0.0102
2478 Beta-lactamase ampC 0.0102
2613 Beta-lactamase ampC 0.0102
2635 Beta-lactamase ampC 0.0102
2700 Beta-lactamase penP 0.0102
5445 Beta-lactamase blaB 0.0102
6019 Beta-lactamase SHV-7 0.0102
6701 Beta-lactamase cphA 0.0102
3810 Catechol O-methyltransferase COMT 0.0092
3760 Penicillin-binding protein 5 precursor dacA 0.0091
709 ATP-sensitive inward rectifier potassium channel 1 KCNJ1 0.0089
3426 Glutamine synthetase glnA 0.0089
3987 Glutamine synthetase GLUL 0.0089
6184 D-alanyl-D-alanine carboxypeptidase dacC dacC 0.0088
867 Penicillin-binding protein 3 pbpC 0.0083
6119 Penicillin-binding protein 3 pbp3 0.0083
7154 Penicillin-binding protein 3 pbp3 0.0083
7157 Penicillin-binding protein 3 LMHCC_2184 0.0083
7162 Penicillin-binding protein 3 pbpB 0.0083
7172 Penicillin-binding protein 3 pbp3 0.0083
6113 MecA PBP2' (penicillin binding protein 2') mecA 0.0082
20 Prostaglandin G/H synthase 1 PTGS1 0.0078
318 Alpha-2A adrenergic receptor ADRA2A 0.0071
1141 Sialidase-1 NEU1 0.0068
64 Neuraminidase NA 0.0068
641 Neuraminidase NA 0.0068
2676 Neuraminidase NA 0.0068
3026 Neuraminidase NA 0.0068
3519 Neuraminidase NA 0.0068
6007 Neuraminidase NA 0.0068
2164 Multidrug resistance-associated protein 4 ABCC4 0.0063
6160 Solute carrier organic anion transporter family member 3A1 SLCO3A1 0.006
6154 Multidrug and toxin extrusion protein 1 SLC47A1 0.0059
6153 Solute carrier organic anion transporter family member 4A1 SLCO4A1 0.0059
632 Alpha-1B adrenergic receptor ADRA1B 0.0056
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0054
5482 Sialidase-2 NEU2 0.0052
556 Alpha-1A adrenergic receptor ADRA1A 0.005
6106 Cytochrome P450 2C18 CYP2C18 0.0048
707 72 kDa type IV collagenase MMP2 0.0048
833 Organic cation/carnitine transporter 1 SLC22A4 0.0048
2461 D-alanyl-D-alanine carboxypeptidase Not Available 0.0046
5756 D-alanyl-D-alanine carboxypeptidase dac 0.0046
3961 G protein-activated inward rectifier potassium channel 4 KCNJ5 0.0046
4924 Cytochrome P450 2C8 CYP2C8 0.0043
65 Matrix metalloproteinase-9 Not Available 0.0039
521 ATP-binding cassette transporter sub-family C member 9 ABCC9 0.0038
132 ATP-binding cassette sub-family A member 1 ABCA1 0.0035
2184 Cystic fibrosis transmembrane conductance regulator CFTR 0.0034
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0033
4118 Cytochrome P450 3A5 CYP3A5 0.0033
866 Large neutral amino acids transporter small subunit 2 SLC7A8 0.0032
238 Peroxisome proliferator-activated receptor gamma PPARG 0.0031
1181 Alpha-1-acid glycoprotein 1 ORM1 0.003
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.003
245 Large neutral amino acids transporter small subunit 1 SLC7A5 0.0029
3876 Aromatic-L-amino-acid decarboxylase DDC 0.0029
6107 Cytochrome P450 3A7 CYP3A7 0.0024
163 D(1B) dopamine receptor DRD5 0.0024
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0023
432 D(4) dopamine receptor DRD4 0.0023
638 D(3) dopamine receptor DRD3 0.0022
776 Bile salt export pump ABCB11 0.0022
862 Multidrug resistance-associated protein 1 ABCC1 0.002
23 D(1A) dopamine receptor DRD1 0.002
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0019
831 D(2) dopamine receptor DRD2 0.0018
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0018
631 3-hydroxy-3-methylglutaryl-coenzyme A reductase HMGCR 0.0017
3387 3-hydroxy-3-methylglutaryl-coenzyme A reductase mvaA 0.0017
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0015
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0014
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.0014
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0014
6024 Cytochrome P450 1A1 CYP1A1 0.0011
6030 Cytochrome P450 2B6 CYP2B6 0.0011
4200 Cytochrome P450 1A2 CYP1A2 0.0009
↑