Disease relevance of Zelitrex

• Treatment with valacyclovir also decreased the rates of CMV viremia and viruria, herpes simplex virus disease, and the use of inpatient medical resources [1].
• Valacyclovir to prevent cytomegalovirus disease after renal transplantation [2].
• Acyclovir is licensed for treatment of varicella and herpes zoster, and acyclovir, valacyclovir, and famciclovir are approved for herpes zoster [3].
• However, valacyclovir had to be stopped after 6 months due to side effects, and the lymphoma reoccurred 3 months later associated with increasing EBVL [4].
• A large-scale, placebo-controlled, dose-ranging trial of peroral valaciclovir for episodic treatment of recurrent herpes genitalis. Valaciclovir HSV Study Group [5].
• In this double-blind study, 87 immunocompromised patients with clinical evidence of localized herpes zoster were randomized to receive oral valacyclovir therapy for 7 days, either 1 g TID or 2 g TID, within 72 h after onset of zoster rash [6].

Psychiatry related information on Zelitrex

• Hallucinations and confusion were more common with valacyclovir treatment, but these events were not severe or treatment-limiting [1].
• Potential benefits of the once-daily regimen of valacyclovir HCl include improved patient compliance [7].

High impact information on Zelitrex

• At six months, the rate of biopsy-confirmed acute graft rejection in the seronegative group was 52 percent among placebo recipients and 26 percent among valacyclovir recipients (P=0.001) [1].
• Randomized study of valacyclovir as prophylaxis against cytomegalovirus reactivation in recipients of allogeneic bone marrow transplants [8].
• Recombinant BPHL exhibited significant hydrolytic activity for both valacyclovir and valganciclovir with specificity constants (kcat/Km), 420 and 53.2 mm-1.s-1, respectively [9].
• Its physiological function is not known; however, it may play a significant role in the biotransformation of valaciclovir to acyclovir [10].
• Accordingly, valaciclovir has the same antiviral activity as acyclovir, but the potential for enhanced clinical activity and/or less frequent administration because of its superior pharmacokinetics [5].

Chemical compound and disease context of Zelitrex

• The comparative effects of famciclovir and valacyclovir on herpes simplex virus type 1 infection, latency, and reactivation in mice [11].
• Preliminary results of a large controlled trial indicate that valaciclovir 1000 mg 3 times daily and famciclovir (the prodrug of penciclovir) 500 mg 3 times daily are of similar efficacy in speeding resolution of acute herpes zoster rash and shortening the duration of postherpetic neuralgia [12].
• A randomized, double-blind trial of valaciclovir prophylaxis for cytomegalovirus disease in patients with advanced human immunodeficiency virus infection. AIDS Clinical Trials Group Protocol 204/Glaxo Wellcome 123-014 International CMV Prophylaxis Study Group [13].
• Once-daily valacyclovir hydrochloride for suppression of recurrent genital herpes [7].
• OBJECTIVE: Ten patients with recurrent ovarian cancer received a combined treatment of optimal tumor debulking, adenovirus-mediated herpes simplex virus thymidine kinase gene therapy (GT), and systemic application of acyclovir or valacyclovir and topotecan [14].
• Prednisolone shortened the time to complete recovery in patients with Bell's palsy, whereas valaciclovir did not affect facial recovery [15].

Biological context of Zelitrex

• Valaciclovir therapy accelerated the resolution of pain (hazard ratio, 1.8; 95% CI, 1.5-2.1) and the time to cessation of viral shedding (hazard ratio, 2.9; 95% CI, 2.1-3.9) [5].
• The favorable safety profile and enhanced acyclovir bioavailability from valaciclovir administration has prompted additional clinical evaluations for zoster and herpes simplex virus treatment, as well as cytomegalovirus suppression in immunocompromised patients [16].
• Variability in valacyclovir bioavailability and the potential for cephalexin-valacyclovir interaction were evaluated [17].
• We conclude that the improved bioavailability previously reported for valacyclovir in plasma results in higher concentrations in CSF, while the CSF/serum AUC ratio remains constant [18].
• These results suggest a stable valacyclovir absorption phenotype, significant interindividual variability, and minimal interaction between these hPEPT1 substrates [17].

Anatomical context of Zelitrex

• Aciclovir and valaciclovir have been examined in randomised, controlled trials in both solid organ and stem cell transplant patients, and were shown to be very effective for the prevention of herpes simplex virus (HSV) and varicella-zoster virus infections [19].
• EBV replication returned in normal tongue epithelial cells after valacyclovir treatment [20].
• Acyclovir levels in serum and cerebrospinal fluid after oral administration of valacyclovir [18].
• In mice that had received valaciclovir therapy, however, infectious virus was repeatedly detected in the trigeminal ganglia and brain stem tissue samples up to 7 days after treatment was discontinued [21].
• In summary, safe treatment of HLP and of EBV replication, with valacyclovir, provides new insight into the mechanisms of EBV persistence in oral mucosa [22].

Associations of Zelitrex with other chemical compounds

• CONCLUSIONS: Valacyclovir and oral ganciclovir are equally effective in the prevention of CMV disease after renal transplantation [23].
• MPA and MPAG pharmacokinetic parameters were not significantly modified following coadministration of MMF with valaciclovir or aciclovir except for MPAG AUC infinity, which was decreased by 12% with valaciclovir [24].
• In study 2, HSV was detected on 3.2% of days among famciclovir recipients and 1.3% of days among valacyclovir recipients, relative risk 2.33 (95% CI, 1.18-4.89) [25].
• BENZ uptake was significantly decreased in Caco-2 and MDCK cells in Na(+)-depleted buffer, whereas VACV uptake only decreased in Caco-2 cells [26].
• Modification of aciclovir by valine esterification, producing valaciclovir, results in significant increases in systemic aciclovir plasma levels [27].

Gene context of Zelitrex

• In contrast, uptake of valacyclovir, L-valyl ester of ACV, was observed only in hOAT3-expressing cells [28].
• We conclude that valacyclovir is a substrate for the peptide transporters PEPT1 and PEPT2 and that a peptide bond is not a prerequisite for recognition as a substrate by the peptide transporters [29].
• The possible involvement of herpesviruses in the pathogenesis of multiple sclerosis (MS) was recently investigated in a clinical trial of valacyclovir in patients with MS [18].
• METHODS: A total of 83 patients were prospectively randomized to 3-month treatment with oral ganciclovir (3 g/day, n=36, GAN) or oral valacyclovir (8 g/day, n=35, VAL) [23].
• We describe the emergence of a new ganciclovir resistance mutation in the UL97 gene of human cytomegalovirus, deletion of codon 601, after valaciclovir and short-term ganciclovir therapy following kidney transplantation [30].

Analytical, diagnostic and therapeutic context of Zelitrex

• Among the seronegative patients, the incidence of CMV disease 90 days after transplantation was 45 percent among placebo recipients and 3 percent among valacyclovir recipients [1].
• CONCLUSIONS: Prophylactic treatment with valacyclovir is a safe and effective way to prevent CMV disease after renal transplantation [1].
• Safety monitoring data from clinical trials of valacyclovir, involving over 3000 immunocompetent and immunocompromised persons receiving long-term therapy for HSV suppression, were analyzed [31].
• Valaciclovir represents and advance in antiherpes drug therapy and is a useful treatment option for patients with herpes zoster or genital herpes [32].
• No significant differences in frequency and quantity of HSV were detected by PCR between the valacyclovir and acyclovir arms [33].

References