Valganciclovir

Valganciclovir

Systematic (IUPAC) name
2-[(2-amino-6-oxo-6,9-dihydro-3H-purin-9-yl)methoxy]-3-hydroxypropyl (2S)-2-amino-3-methylbutanoate
Clinical data
Trade names	Valcyte
AHFS/Drugs.com	monograph
MedlinePlus	a605021
Pregnancy cat.	C(US)
Legal status	POM (UK) ℞-only (US)
Routes	Oral
Pharmacokinetic data
Bioavailability	60%
Protein binding	1-2%
Metabolism	Hydrolysed to ganciclovir
Half-life	4 hours
Excretion	Renal
Identifiers
CAS number	175865-59-5 N
ATC code	J05AB14
PubChem	CID 64147
DrugBank	DB01610
ChemSpider	57721 Y
UNII	GCU97FKN3R Y
ChEMBL	CHEMBL1201314 N
Chemical data
Formula	C14H22N6O5
Mol. mass	354.362 g/mol
SMILES	eMolecules & PubChem
InChI 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 Y Key:WPVFJKSGQUFQAP-GKAPJAKFSA-N Y
N(what is this?)  (verify)

Valganciclovir hydrochloride (Valcyte, manufactured by Hoffmann–La Roche (Roche). Also Cymeval, Valcyt, Valixa, Darilin, Rovalcyte, Valcyte, Patheon, Syntex^[1]) is an antiviral medication used to treat cytomegalovirus infections. As the L-valyl ester of ganciclovir, it is actually a prodrug for ganciclovir.^[2] After oral administration, it is rapidly converted to ganciclovir by intestinal and hepatic esterases.

Administration

Orally, available in 450 mg pink tablets. For patients who have received a transplant, the recommended dose is 900 mg once daily, starting within 10 days of transplantation and continuing until 100 days post transplantation. HIV patients might initially need to take the dose 900 mg twice daily for the first 3 weeks.^[3]

Pharmacokinetics

1. Oral bioavailability is approximately 60%. Fatty foods significantly increase the bioavailability and the peak level in the serum.
2. It takes about 2 hours to reach maximum concentrations in the serum.
3. Valganciclovir is eliminated as ganciclovir in the urine, with a half-life of about 4 hours in people with normal kidney function.
4. The mechanism of this drug is activation via thymidine kinase enzyme. The phosphotransferase enzyme can likewise activate valganciclovir.

Side effects

• Blood: neutropenia, anemia, low platelets. Myelosuppression is one of the main side effects that may limit prolonged use of valganciclovir.
• Gastrointestinal: diarrhea, nausea, vomiting, abdominal pain.
• Central nervous system: fever, headache, insomnia, paresthesia, and peripheral neuropathy.
• Ocular: retinal detachment

Alternative uses

It has been proposed that valganciclovir could be used in the treatment of chronic fatigue syndrome. Following some reported success in 9 out of 12 patients at Stanford University in California, a follow-up double-blind, controlled study of 30 patients was completed, and although data has not yet been released, according to the Virus Induced CNS Dysfunction Association, "the data Dr. Montoya presented at the 2008 International Conference on HHV-6&7 indicated that patients on Valcyte experienced significant cognitive improvement.", especially for those with elevated antibody levels to HHV-6 and EBV (VCA and EA) ^[4][5]

Price and patent status

Roche's Valcyte is protected by patent. However a generic version manufactured by Japanese-owned Indian company Daiichi-Ranbaxy was found by the District Court of New Jersey, USA not to infringe Roche's patent.^[6]

The price of a four-month course of valganciclovir from Roche is about US$8,500 in high-income countries, $6,000 in India. However, the valganciclovir patent was rejected by the Indian Patent Office^[7] in 2010, although Roche may appeal the rejection.

References

1. ^ Drugs.about list of names for valganciclovir
2. ^ Sugawara M, Huang W, Fei YJ, et al. Transport of valganciclovir, a ganciclovir prodrug, via peptide transporters PEPT1 and PEPT2. J Pharm Sci. 2000;89(6):781-9.
3. ^ electronic Medicines Compendium
4. ^ http://www.vicd.info/clinicaltrial.html
5. ^ http://www.scivee.tv/node/7026
6. ^ US Court rules Ranbaxy's generic valganciclovir does not infringe Roche's Valcyte patent
7. ^ Valganciclovir rejected by the Indian Patent Office

• Kogelnik AM et al. Use of valganciclovir in patients with elevated antibody titers against Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV) who were experiencing central nervous system dysfunction including long-standing fatigue. J Clin Virol. 2006;37(S1):S33-S38.
• Paltiel AD et al. Preevaluation of clinical trial data: the case of preemptive cytomegalovirus therapy in patients with human immunodeficiency virus. Clin Infect Dis. 2001;32(5):783-93.
• Pescovitz MD et al. Valganciclovir results in improved oral absorption of ganciclovir in liver transplant recipients. Antimicrob Agents Chemother. 2000;44(10):2811-5.
• Reusser P. Antiviral therapy: current options and challenges. Schweiz Med Wochenschr. 2000;130(4):101-12.