Disease relevance of Valcyt

• Cytomegalovirus-induced hemorrhagic cystitis in AIDS patient treated successfully with valganciclovir [1].
• Successful oral valganciclovir treatment of cytomegalovirus infection during Campath-1H therapy [2].
• Therefore, when used as prophylaxis against CMV infection and disease in high-risk solid organ transplant recipients or as induction and maintenance therapy of CMV retinitis in patients with AIDS, oral valganciclovir is an attractive alternative to other available anti-CMV drugs [3].
• EBV infection was common, although incidence of high-level EBV DNAemia was low, especially in patients who received valganciclovir prophylaxis [4].
• Viremia was suppressed during prophylaxis when exposure to ganciclovir was 40-50 microg.h/ml, AUCs typical of those achieved in valganciclovir-treated patients [5].

Psychiatry related information on Valcyt

• The simple and convenient once-daily valganciclovir regimen offers potential for improved patient compliance [3].

High impact information on Valcyt

• CONCLUSION: Similar reduction of CMV DNA load was observed during pre-emptive treatment with oral valganciclovir and iv ganciclovir in transplant recipients [6].
• We conclude that BPHL may be an important enzyme activating valacyclovir and valganciclovir in humans and an important new target for prodrug design [7].
• The pharmacokinetics of valganciclovir in patients with renal impairment is not known [8].
• Characterization of human cytomegalovirus (HCMV) UL97 mutations found in a valganciclovir/oral ganciclovir prophylactic trial by use of a bacterial artificial chromosome containing the HCMV genome [9].
• Valganciclovir: a review of its use in the management of CMV infection and disease in immunocompromised patients [3].

Chemical compound and disease context of Valcyt

• DISCUSSION: Drugs taken by this child (acyclovir, valganciclovir, omeprazole) have been reported to induce neurotoxicity, with the pharmacokinetics of the first 2 being altered by renal failure [10].
• The patient was then treated with a novel treatment consisting of 5-fluorouracil plus valproic acid and subsequent valganciclovir to induce lytic EBV replication [11].
• Recently, several small case series and case reports have described the use of newer oral antivirals such as valacyclovir, famciclovir or valganciclovir, alone or in combination with adjunctive intravitreal foscarnet or ganciclovir injections for the treatment of acute retinal necrosis (1-4) [12].
• The success rate of viremia eradication at Day 21 was 45.1% for valganciclovir and 48.4% for ganciclovir (95% CI -14.0% to +8.0%), and at Day 49; 67.1% and 70.1%, respectively (p = NS) [13].

Biological context of Valcyt

• The oral bioavailability of ganciclovir after oral valganciclovir administration is high [14].
• Kinetics of cytomegalovirus load decrease in solid-organ transplant recipients after preemptive therapy with valganciclovir [15].
• Development of new cytomegalovirus UL97 and DNA polymerase mutations conferring drug resistance after valganciclovir therapy in allogeneic stem cell recipients [16].
• PURPOSE: To determine whether treatment with valganciclovir will improve visual acuity in eyes with immune recovery uveitis complicated by macular edema [17].
• Noninferiority of 900 mg of valganciclovir relative to intravenous ganciclovir was concluded if the lower limit of the 1-sided 95% confidence interval of the ratio of least-square means of the ganciclovir area under the curve (AUC) for the 2 study drugs was >80% [18].

Anatomical context of Valcyt

• Rate of emergence of cytomegalovirus (CMV) mutations in leukocytes of patients with acquired immunodeficiency syndrome who are receiving valganciclovir as induction and maintenance therapy for CMV retinitis [19].
• Pharmacokinetics of oral valganciclovir and intravenous ganciclovir administered to prevent cytomegalovirus disease in an adult patient receiving small-intestine transplantation [20].
• METHODS: The interaction of amino acid esters and valganciclovir with the cloned rat ATB(0,+) was evaluated in a mammalian cell expression system and in the Xenopus oocyte expression system [21].
• STUDY DESIGN: Patients with high IgG antibody titers against HHV-6 and EBV who were suffering from central nervous system dysfunction and debilitating fatigue for more than one year (median 3 years, range 1-8 years) were treated with 6 months of valganciclovir in an open label study [22].
• Valganciclovir is safe and effective as pre-emptive therapy for CMV infection in allogeneic hematopoietic stem cell transplantation [23].

Associations of Valcyt with other chemical compounds

• Unexpected rate of severe leucopenia with the association of mycophenolate mofetil and valganciclovir in kidney transplant recipients [24].
• R1518 was also found to inhibit the permeability of valganciclovir and cephalexin [25].
• In neonates with symptomatic congenital CMV disease, valganciclovir oral solution provides plasma concentrations of ganciclovir comparable to those achieved with administration of intravenous ganciclovir [26].

Gene context of Valcyt

• The transport of valganciclovir via PEPT1 was investigated directly in PEPT1-expressing Xenopus laevis oocytes with an electrophysiological approach [27].
• Although the viral protein kinase UL97 has been exploited as an activator of ganciclovir and its prodrug valganciclovir, a new inhibitor maribavir (benzamidavir) has been shown to be a highly potent inhibitor of this enzyme [28].
• AIDS patients (median CD4 lymphocyte count of 140 cells/microL) with treated CMV retinitis (N = 212) received 900-mg once-daily valganciclovir maintenance therapy with courses of 900-mg twice-daily valganciclovir induction therapy as needed to treat progression [29].
• Analysis of cytomegalovirus DNA polymerase (UL54) mutations in solid organ transplant patients receiving valganciclovir or ganciclovir prophylaxis [30].
• CASE SUMMARY: A 13-year-old boy with acute lymphoblastic leukemia was treated for cytomegalovirus retinitis with valganciclovir 450 mg every 2 days in the course of hematopoietic stem cell transplantation [10].

Analytical, diagnostic and therapeutic context of Valcyt

• METHODS: To facilitate the introduction of valganciclovir, a therapeutic guideline was developed to use this drug under controlled conditions with regard to safety in renal/renal-pancreas transplant recipients requiring CMV therapy [6].
• Valganciclovir and ganciclovir serum concentrations were measured after oral administration of 900 mg of valganciclovir [8].
• Efficacy of valganciclovir administered as preemptive therapy for cytomegalovirus disease in liver transplant recipients: impact on viral load and late-onset cytomegalovirus disease [31].
• A recent randomised, double-blind study of valganciclovir in 364 D+/R- (intent-to-treat population) SOT recipients provided valuable data on which a population pharmacokinetic analysis was performed [32].
• Absence of cytomegalovirus-resistance mutations after valganciclovir prophylaxis, in a prospective multicenter study of solid-organ transplant recipients [33].

References