Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Valganciclovir”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1999

Pharmacokinetics of valganciclovir and ganciclovir following multiple oral dosages of valganciclovir in HIV- and CMV-seropositive volunteers.

OBJECTIVE: Ganciclovir is commonly used in the treatment of cytomegalovirus (CMV) disease in patients who are immunocompromised and for the prevention of CMV disease in solid organ transplant recipients. Owing to limited bioavailability and saturable absorption, the use of oral ganciclovir in CMV retinitis is restricted to maintenance therapy only. As induction therapy must be given intravenously, an oral formulation which could be used for induction would offer significant benefits. A previous study of valganciclovir, a valyl ester prodrug of ganciclovir showed a 10-fold increase in plasma ganciclovir concentrations compared with the oral formulation. However, before studies can be conducted to confirm the utility of oral valganciclovir for the treatment and prevention of CMV disease, a dose must be selected for use in these studies. This study was designed to investigate the pharmacokinetics of ganciclovir and valganciclovir. DESIGN AND PARTICIPANTS: The study was an open-label, randomised, 4-way crossover, dose-ranging pharmacokinetic study, conducted in 39 patients who were HIV- and CMV-seropositive. The participants were randomised to one of 2 groups: fasted (n = 19) and fed (n = 20). In both groups, participants received 450, 875, 1750 and 2625 mg oral valganciclovir once daily for 3 days in a randomised order. RESULTS: In the 32 participants who completed the study, valganciclovir was rapidly absorbed and converted into ganciclovir (maximum ganciclovir concentrations occurred after 1.0 to 1.75 hours in the fasted group and 1.5 to 2.0 hours in the fed group). Systemic exposure to valganciclovir was low [with an area under the concentration-time curve to 24 hours (AUC24) of 1.3 to 2.5% that of ganciclovir]. The mean plasma concentrations of ganciclovir were dose-related. Peak concentrations of ganciclovir were achieved approximately 30 minutes after those for valganciclovir. In the fed state, the AUC24 of ganciclovir increased proportionally with dose. The mean AUC24 values for ganciclovir were slightly higher following food (24 to 56%) than in the fasted state. Based on linear regression of AUC24 values from the fed group, a dose of valganciclovir of 900 mg/day is expected to produce a daily exposure (AUC24) comparable with an intravenous dose of ganciclovir 5 mg/kg/day. CONCLUSIONS: These results show that once daily oral valganciclovir can produce exposures of ganciclovir (AUC24) exceeding those attained using intravenous ganciclovir 10 mg/kg. This suggests that oral valganciclovir may be suitable in many circumstances currently requiring intravenous ganciclovir, allowing for more convenience in the management of patients with CMV retinitis by utilising a 2 or 4 tablet daily regimen to cover all phases of treatment.

Administration, Oral↗
PubMed2004

Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients.

We compared the efficacy and safety of valganciclovir with those of oral ganciclovir in preventing cytomegalovirus (CMV) disease in high-risk seronegative solid organ transplant (SOT) recipients of organs from seropositive donors (D+/R-). In this randomised, prospective, double-blind, double-dummy study, 364 CMV D+/R- patients received valganciclovir 900 mg once daily or oral ganciclovir 1000 mg three times a day (tid) within 10 days of transplant and continued through 100 days. CMV disease, plasma viremia, acute graft rejection, graft loss and safety were analyzed up to 6 and 12 months post-transplant. Endpoint committee-defined CMV disease developed in 12.1% and 15.2% of valganciclovir and ganciclovir patients, respectively, by 6 months, though with a difference in the relative efficacy of valganciclovir and ganciclovir between organs (i.e. an organ type-treatment interaction). By 12 months, respective incidences were 17.2% and 18.4%, and the incidence of investigator-treated CMV disease events was comparable in the valganciclovir (30.5%) and ganciclovir (28.0%) arms. CMV viremia during prophylaxis was significantly lower with valganciclovir (2.9% vs. 10.4%; p=0.001), but was comparable by 12 months (48.5% valganciclovir vs 48.8% ganciclovir). Time-to-onset of CMV disease and to viremia were delayed with valganciclovir; rates of acute allograft rejection were generally lower with valganciclovir. Except for a higher incidence of neutropenia with valganciclovir (8.2%, vs 3.2% ganciclovir) the safety profile was similar for both drugs. Overall, once-daily oral valganciclovir was as clinically effective and well-tolerated as oral ganciclovir tid for CMV prevention in high-risk SOT recipients.

Administration, Oral↗
PubMed2005

Pharmacokinetic profile of ganciclovir after its oral administration and from its prodrug, valganciclovir, in solid organ transplant recipients.

BACKGROUND: Valganciclovir (Valcyte) has recently been approved for the prevention of cytomegalovirus (CMV) disease in high-risk (CMV donor positive [D+]/recipient negative [R-]) solid organ transplant (SOT) recipients. Large-scale studies describing the pharmacokinetics of valganciclovir in SOT recipients are lacking. 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. METHODS: The pharmacokinetics of ganciclovir from oral ganciclovir (Cymevene, 1000 mg three times daily) and from valganciclovir (900 mg once daily) were described with plasma levels from 240 patients (1181 datapoints describing 449 pharmacokinetic profiles) using nonlinear mixed-effects modelling (NONMEM) software. A two-compartment pharmacokinetic model with separate absorption/metabolism and absorption parameters for valganciclovir and ganciclovir, respectively, was developed. RESULTS: Exposure to ganciclovir from valganciclovir averaged 1.65-fold greater than that from oral ganciclovir (95% CI 1.58, 1.81); respective daily area under the plasma concentration-time curve values were 46.3 +/- 15.2 microg . h/mL and 28.0 +/- 10.9 microg . h/mL. The relative systemic exposure of ganciclovir was approximately 8-fold higher from valganciclovir than oral ganciclovir. Exposure to ganciclovir from valganciclovir was similar among liver, heart and kidney transplant recipients (46.0 +/- 16.1, 40.2 +/- 11.8 and 48.2 +/- 14.6 microg . h/ mL, respectively). Adherence to the prescribed dosing regimens, which were reduced for renal impairment, gave consistent exposure to ganciclovir. CONCLUSION: Oral valganciclovir produces exposures of ganciclovir exceeding those attained with oral ganciclovir, but in line with those reported after standard intravenous administration of ganciclovir. This indicates that oral valganciclovir is suitable in circumstances requiring prophylactic use of ganciclovir and allows for more convenient management of patients at risk of CMV disease.

Administration, Oral↗
PubMed2005

Neurotoxicity related to valganciclovir in a child with impaired renal function: usefulness of therapeutic drug monitoring.

OBJECTIVE: To report a case of neurotoxicity related to antiviral drugs, discuss the involvement of concomitant medications, and document the pharmacokinetics of ganciclovir (administered as valganciclovir) in a child with impaired renal function. 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. Concomitant medication included omeprazole, furosemide, and acetaminophen. During treatment, when creatinine clearance decreased to 20 mL/min, the child presented with acute neurotoxicity, consisting of mental confusion and hallucinations, which resolved when all medications were stopped. Valganciclovir therapeutic monitoring showed high ganciclovir concentrations in the plasma (3.85 microg/mL) and cerebrospinal fluid (2.6 microg/mL) 48 hours after the last valganciclovir dose. After recovery of neurologic function, valganciclovir was resumed at a lower dosage (225 mg twice a week) with therapeutic drug monitoring and was well tolerated. However, the cytomegalovirus infection was not resolved. The leukemia relapsed, and the patient had terminal renal failure and died. The Naranjo probability scale indicated a probable relationship between valganciclovir and neurotoxicity. 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. At the time when acyclovir was first administered, symptoms of neurotoxicity were already apparent. Moreover, plasma concentrations of ganciclovir were very high during the course of the neurotoxicity. Thus, the adverse effects seemed related to an overdosage of valganciclovir and were worsened by the addition of acyclovir. CONCLUSIONS: This case is informative because few clinical and pharmacokinetic data are available concerning the use of valganciclovir in children. A study should be performed to determine the proper pediatric dose of valganciclovir with and without renal impairment to prevent the occurrence of adverse effects.

Adolescent↗
PubMed2003

Valganciclovir: new preparation. CMV retinitis: a simpler, oral treatment.

For AIDS patients with cytomegalovirus (CMV) retinitis, the standard initial treatment has so far been ganciclovir or foscarnet, both of which are infused intravenously. The choice between these two antiviral agents is based on their differing side effects. Maintenance treatment is based on ganciclovir or foscarnet, but both these drugs must be given as daily intravenous infusions. Oral ganciclovir is less effective. Intraocular maintenance treatment in appropriate only for patients with localised infections and a low risk of relapse. Valganciclovir can be taken orally for both initial and maintenance treatment of CMV retinitis. Valganciclovir has good bioavailability and is rapidly metabolised into ganciclovir. A comparative randomised trial in 160 patients showed that oral valganciclovir is as effective as intravenous ganciclovir when used as an initial treatment. There are no comparative trials of oral valganciclovir as a maintenance treatment, but non comparative data and pharmacokinetic studies suggest that oral valganciclovir is about as effective as intravenous ganciclovir. The adverse effects of oral valganciclovir are similar to those of intravenous ganciclovir, except that the oral route avoids the risk of local complications at the infusion site. Valganciclovir causes more frequent diarrhoea and oral candidosis than intravenous ganciclovir. In practice, for patients with CMV retinitis who require systemic treatment, oral valganciclovir is easier to use and, in our opinion, should now replace IV ganciclovir for both initial and maintenance treatment. The convenience of oral valganciclovir should also limit the use of purely intraocular treatment of CMV retinitis.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Oral valganciclovir as pre-emptive therapy has similar efficacy on cytomegalovirus DNA load reduction as intravenous ganciclovir in allogeneic stem cell transplantation recipients.

The efficacy and safety of oral valganciclovir was compared to ganciclovir i.v. in pre-emptive treatment of cytomegalovirus (CMV) in T-cell-depleted allogeneic stem cell transplant (allo-SCT) recipients. A therapeutic guideline was developed to allow the safe application of valganciclovir in allo-SCT recipients requiring CMV therapy. In total, 107 consecutive transplant recipients were evaluated. Cytomegalovirus DNA load in plasma was monitored longitudinally; details on antiviral therapy and treatment responses were analyzed retrospectively. Fifty-seven CMV treatment episodes were recorded in 34 patients: 20 with valganciclovir (900 mg twice-daily) and 37 with ganciclovir (5 mg/kg twice-daily). Median CMV DNA load reduction was 0.079 and 0.069 log10 copies/ml/day in the ganciclovir and valganciclovir group, respectively. Good response on CMV DNA load (reduction below 3.0 log10 copies/ml) was observed in 75.7% of ganciclovir and 80.0% of valganciclovir treatment episodes. Severe adverse effects were not observed and CMV-related disease did not occur. However, the percentage of patients receiving erythrocyte transfusion was higher in the group of patients receiving ganciclovir as compared to valganciclovir (41 versus 20%, P=0.116). In conclusion, pre-emptive treatment with valganciclovir and ganciclovir, led to similar reduction of CMV DNA load. Oral valganciclovir is an attractive and safe alternative for pre-emptive CMV treatment in T-cell-depleted allo-SCT recipients.

Administration, Oral↗
PubMed2002

A controlled trial of valganciclovir as induction therapy for cytomegalovirus retinitis.

BACKGROUND: Valganciclovir is an orally administered prodrug that is rapidly hydrolyzed to ganciclovir. We compared the effects of oral valganciclovir with those of intravenous ganciclovir as induction therapy for newly diagnosed cytomegalovirus retinitis in 160 patients with the acquired immunodeficiency syndrome (AIDS). METHODS: The primary end point was photographically determined progression of cytomegalovirus retinitis within four weeks after the initiation of treatment. Secondary end points included the achievement of a prospectively defined satisfactory response to induction therapy and the time to progression of cytomegalovirus retinitis. After four weeks, all patients received valganciclovir as maintenance therapy. RESULTS: Eighty patients were randomly assigned to each treatment group. Of the patients who could be evaluated, 7 of 70 assigned to intravenous ganciclovir (10.0 percent) and 7 of 71 assigned to oral valganciclovir (9.9 percent) had progression of cytomegalovirus retinitis during the first four weeks (difference in proportions, 0.1 percentage point; 95 percent confidence interval, -9.7 to 10.0). Forty-seven of 61 patients (77.0 percent) assigned to intravenous ganciclovir and 46 of 64 (71.9 percent) assigned to valganciclovir had a satisfactory response to induction therapy (difference in proportions, 5.2 percentage points; 95 percent confidence interval, -20.4 to 10.1). The median times to progression of retinitis were 125 days in the group assigned to intravenous ganciclovir and 160 days in the group assigned to oral valganciclovir. The mean values for the area under the curve for the ganciclovir dosage interval were similar at both induction doses and maintenance doses. The frequency and severity of adverse events were similar in the two treatment groups. CONCLUSIONS: Orally administered valganciclovir appears to be as effective as intravenous ganciclovir for induction treatment and is convenient and effective for the long-term management of cytomegalovirus retinitis in patients with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed2000

Transport of valganciclovir, a ganciclovir prodrug, via peptide transporters PEPT1 and PEPT2.

In clinical trials, valganciclovir, the valyl ester of ganciclovir, has been shown to enhance the bioavailability of ganciclovir when taken orally by patients with cytomegalovirus infection. We investigated the role of the intestinal peptide transporter PEPT1 in this process by comparing the interaction of ganciclovir and valganciclovir with the transporter in different experimental systems. We also studied the interaction of these two compounds with the renal peptide transporter PEPT2. In cell culture model systems using Caco-2 cells for PEPT1 and SKPT cells for PEPT2, valganciclovir inhibited glycylsarcosine transport mediated by PEPT1 and PEPT2 with K(i) values (inhibition constant) of 1.68+/-0.30 and 0.043+/- 0.005 mM, respectively. The inhibition by valganciclovir was competitive in both cases. Ganciclovir did not interact with either transporter. Similar studies done with cloned PEPT1 and PEPT2 in heterologous expression systems yielded comparable results. The transport of valganciclovir via PEPT1 was investigated directly in PEPT1-expressing Xenopus laevis oocytes with an electrophysiological approach. Valganciclovir, but not ganciclovir, induced inward currents in PEPT1-expressing oocytes. These results demonstrate that the increased bioavailability of valganciclovir is related to its recognition as a substrate by the intestinal peptide transporter PEPT1. This prodrug is also recognized by the renal peptide transporter PEPT2 with high affinity.

Animals↗
PubMed2006

Pharmacokinetics of ganciclovir after oral valganciclovir versus intravenous ganciclovir in allogeneic stem cell transplant patients with graft-versus-host disease of the gastrointestinal tract.

The pharmacokinetics of ganciclovir after oral valganciclovir versus intravenous ganciclovir were compared in allogeneic stem cell transplant recipients with stable graft-versus-host disease of the gastrointestinal tract. Twenty-two evaluable adult patients were randomized to receive a single dose of open-label study drug (900 mg of oral valganciclovir or 5 mg/kg of intravenous ganciclovir). After a washout period of 2 to 7 days, patients were crossed over to receive the alternate study drug. Ganciclovir and valganciclovir concentrations in plasma were measured over 24 hours after dosing. 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%. Valganciclovir was found to be rapidly absorbed and converted into ganciclovir. The ganciclovir exposure after 900 mg of valganciclovir noninferior to that of intravenous ganciclovir (AUC0-infinity, 52.1 and 53.8 microg.h/mL, respectively; 95% confidence interval of the ratio of least square means of AUC0-infinity, 82.48%-118.02%). Oral valganciclovir could be a useful alternative to intravenous ganciclovir in certain stable stem cell transplant patients who require prophylaxis or preemptive therapy for cytomegalovirus infection.

Administration, Oral↗
PubMed2006

Efficacy of valganciclovir in the treatment of cytomegalovirus disease in kidney and pancreas transplant recipients.

Cytomegalovirus (CMV) disease is relatively common following solid organ transplant, particularly if a serologically negative recipient receives an organ from a serologically positive donor (D+/R-). Although valganciclovir is approved for the treatment of CMV retinitis in AIDS patients and is used for the prophylaxis against CMV infection in solid organ transplant patients, the current standard treatment for CMV disease in solid organ transplant recipients remains intravenous ganciclovir. We retrospectively reviewed our experience using valganciclovir as treatment for CMV disease in CMV D+/R- kidney and/or pancreas transplant recipients from March 2002 to June 2005. A total of 37 cases with primary CMV disease were diagnosed and treated with either intravenous ganciclovir as induction followed with valganciclovir or valganciclovir from the beginning. We compared clinical outcomes and viremia between the two groups. Our data suggest that valganciclovir is an effective treatment modality for primary CMV disease in kidney and/or pancreas transplant recipients. It led to the resolution of disease and undetectable viremia. Valganciclovir allowed for early initiation of treatment and for treatment to be given as an outpatient. These advantages of valganciclovir have both health and economic impact for patients with CMV disease.

Adult↗
PubMed2004

Transport of amino acid esters and the amino-acid-based prodrug valganciclovir by the amino acid transporter ATB(0,+).

PURPOSE: The purpose of this study was to analyze the transport of amino acid esters and the amino-acid-based prodrug valganciclovir by the Na(+)/Cl(-)-coupled amino acid transporter ATB(0,+). 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. RESULTS: In mammalian cells, expression of ATB(0,+) induced glycine uptake. This uptake was inhibited by valine and its methyl, butyl, and benzyl esters. The benzyl esters of other neutral amino acids were also effective inhibitors. Valganciclovir, the valyl ester of ganciclovir, was also found to inhibit ATB(0,+)-mediated glycine uptake competitively. Exposure of ATB(0,+)-expressing oocytes to glycine induced inward currents. Exposure to different valyl esters (methyl, butyl, and benzyl), benzyl esters of various neutral amino acids, and valganciclovir also induced inward currents in these oocytes. The current induced by valganciclovir was saturable with a K0.5 value of 3.1+/-0.7 mM and was obligatorily dependent on Na+ and Cl-. The Na+:Cl-:valganciclovir stoichiometry was 2 or 3:1:1. CONCLUSIONS: Amino acid esters and the amino-acid-based prodrug valganciclovir are transported by ATB(0,+). This shows that ATB(0,+) can serve as an effective delivery system for amino acid-based prodrugs.

Amino Acid Transport System ASC↗
PubMed2002

Pharmacokinetics of valganciclovir and ganciclovir in renal impairment.

BACKGROUND: Valganciclovir is the oral prodrug of ganciclovir. The pharmacokinetics of valganciclovir in patients with renal impairment is not known. Furthermore, it is not known whether there are any pharmacokinetic differences between patients who are positive for human immunodeficiency virus (HIV) and cytomegalovirus (CMV) and healthy subjects. METHODS: A total of 44 patients were included-18 with mild, medium, or severe renal impairment; 6 with end-stage renal disease who were on long-term hemodialysis; 8 HIV/CMV-positive patients with normal renal function; and 12 healthy subjects serving as controls. Valganciclovir and ganciclovir serum concentrations were measured after oral administration of 900 mg of valganciclovir. Pharmacokinetic parameters were estimated by means of noncompartmental and compartmental methods. RESULTS: After oral administration of the prodrug valganciclovir, ganciclovir bioavailability was 60% and ganciclovir concentrations were higher (maximum concentration [C(max)], 8.5 microg/mL versus 5.8 microg/mL) and appeared later (time to maximum concentration [T(max)], 4.3 versus 2.0 hours) in patients with severe renal impairment compared with healthy subjects. The elimination half-life (t(1/2)) of ganciclovir was longer in patients with renal failure (t(1/2) of 68.1 hours in patients with end-stage renal disease compared with 3.5 hours in healthy subjects). Ganciclovir clearance was correlated with creatinine clearance (r = 0.975). Hemodialysis removed 50% of ganciclovir. We observed no differences in pharmacokinetics between HIV/CMV-positive patients and healthy subjects. A 2-compartment model with zero-order input and first-order elimination proved to be the most appropriate model for ganciclovir after oral administration of valganciclovir. CONCLUSIONS: The dosage of valganciclovir has to be adjusted to the degree of renal impairment. Dosage adjustment is not necessary for HIV/CMV-positive patients.

AIDS-Related Opportunistic Infections↗
PubMed2005

Efficacy of valganciclovir administered as preemptive therapy for cytomegalovirus disease in liver transplant recipients: impact on viral load and late-onset cytomegalovirus disease.

BACKGROUND: The efficacy of valganciclovir used as preemptive therapy for cytomegalovirus (CMV) disease in liver transplant recipients is not known. METHODS: Between 1996 and 2004, surveillance testing using CMV antigenemia was performed at weeks 2, 4, 6, 8, 10, 12, and 16 posttransplant. A total of 28.8% (17/59) of the patients from 2001 to 2004 with antigenemia who received valganciclovir as preemptive therapy were compared with 26.2% (21/80) of the patients from 1996 to 2000 who received oral ganciclovir as preemptive therapy. RESULTS: The mean decline in the antigenemia level after initiation of valganciclovir and oral ganciclovir was 80.5% versus 50.7% at 1 week, 99.5% versus 89.4% at 2 weeks, and 100% versus 97.7% at 4 weeks, respectively. A higher proportion of patients who received valganciclovir (64.7%) belonged to the high-risk group (R-/D+) than patients who received oral ganciclovir (33.3%, P=0.10). Recurrent shedding was documented in 47.1% (8/17) of the patients in the valganciclovir group and 28.6% (6/21) of the patients in the oral ganciclovir group (P>0.20). Recurrent shedding correlated significantly with R-/D+ CMV serostatus and baseline CMV antigenemia level, regardless of the study group. No patient in either group developed CMV disease during or after the period of surveillance monitoring. The incidence of opportunistic infections and patient outcome did not differ for the valganciclovir group versus the oral ganciclovir group or patients without CMV infection (P>0.20). CONCLUSION: Antigenemia-directed valganciclovir as preemptive therapy seems to be effective for the prevention of CMV disease in liver transplant recipients, including high-risk patients.

Adult↗
PubMed2001

Valganciclovir.

Valganciclovir is a prodrug of ganciclovir which has been developed for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. Oral valganciclovir is rapidly absorbed and hydrolysed to ganciclovir. The oral bioavailability of ganciclovir after oral valganciclovir administration is high. Oral valganciclovir 900 mg provides a daily exposure of ganciclovir comparable to that of intravenous ganciclovir 5 mg/kg. A single, randomised, nonblind study indicated that oral valganciclovir (900mg twice daily for 3 weeks then 900 mg once daily) and intravenous ganciclovir (5 mg/kg twice daily for 3 weeks then 5 mg/kg once daily) were equally effective in the treatment of newly diagnosed CMV retinitis in 160 patients with AIDS. Valganciclovir appears to have a similar tolerability profile to intravenous ganciclovir during induction therapy in patients with AIDS and newly diagnosed CMV retinitis. During maintenance therapy with valganciclovir, the most commonly reported adverse events included neutropenia, anaemia, thrombocytopenia, gastrointestinal (including diarrhoea, nausea, vomiting and abdominal pain), fever, headache, insomnia, peripheral neuropathy, paraesthesia and retinal detachment.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Initial experience with oral valganciclovir for pre-emptive cytomegalovirus therapy after lung transplantation.

BACKGROUND: The most common opportunistic viral pathogen after lung transplantation is cytomegalovirus (CMV). Oral valganciclovir, a prodrug of ganciclovir, has been introduced as a potential drug for prophylaxis and treatment of CMV infection and disease in lung transplantation. The goal of this study was to describe our initial experience with oral valganciclovir for pre-emptive treatment of CMV infections after lung transplantation. METHODS AND PATIENTS: We summarize our experience with 19 patients who underwent lung transplantation and received pre-emptive oral valganciclovir therapy in the situation of positive CMV polymerase chain reaction (PCR) in either plasma or bronchoalveolar lavage. None of the patients presented with manifest CMV disease. Treatment dosage of valganciclovir was 450 mg to 1800 mg daily, depending on renal function and white blood count. Treatment was continued until the CMV PCR became negative, in any case for a period of at least 14 days. RESULTS: Three patients received two courses of pre-emptive oral valganciclovir; 16 patients were treated once. Eleven patients (57.9%) were treated because of a positive plasma CMV PCR; in eight patients (42.1%) the PCR was positive only in bronchoalveolar lavage. Therapy was initiated 896 +/- 1186 days (range, 108-3911) after transplantation with a mean CMV PCR of 45,536 +/- 149,294 copies (range, 426-706,000). In all cases the PCR fell below detectability (<400 copies) after a period of 22 +/- 10 days of treatment (range, 7-50 days). Mild to moderate leucopenia was observed in seven patients (36.8%) during treatment. None of the patients developed new onset of other potentially drug-related disorders such as neutropenia, anemia, deterioration of renal function or gastrointestinal disorder. CONCLUSIONS: Pre-emptive therapy with oral valganciclovir for CMV infections detected by PCR in either plasma or bronchoalveolar lavage after lung transplantation seems to be efficacious and safe. However, regular blood counts should be performed to detect developing leucopenia.

Administration, Oral↗
PubMed2005

Does valganciclovir hydrochloride (valcyte) provide effective prophylaxis against cytomegalovirus infection in liver transplant recipients?

INTRODUCTION: Cytomegalovirus (CMV) infection after solid organ transplantation is one of the most common viral infections, causing significant morbidity and mortality if not treated promptly. Ganciclovir has proven to be effective for the prophylaxis and treatment of CMV. However, oral absorption of ganciclovir is poor. Recently, oral administration of valganciclovir hydrochloride (Valcyte) has been observed to display 10-fold better absorption than oral ganciclovir. Valganciclovir has increasingly been used as prophylaxis against CMV after solid organ transplantation. The purpose of this study was to examine the efficacy of valganciclovir prophylaxis therapy after primary liver transplantation. PATIENTS AND METHODS: Between July 2001 and May 2003, 203 consecutive liver transplant recipients, including 129 men and 74 women of overall mean age 53 +/- 11 years, received valganciclovir (900 mg/d or 450 mg every other day depending on renal function) for 3 to 6 months after primary liver transplantation. All patients were followed up for a minimum of 6 months. Mean follow-up was 19 +/- 5.8 months. CMV DNA in peripheral blood was tested using polymerase chain reaction (PCR) amplification. Symptomatic CMV was stratified according to the CMV immunoglobulin (Ig)G status of the donor and recipient at the time of liver transplantation. Donors and recipients were classified preoperatively into groups according to the presence or absence of CMV as follows: group 1 (n = 73; donor CMV+, recipient CMV+); group 2 (n = 41; donor CMV-, recipient CMV+); group 3 (n = 54; donor CMV+, recipient CMV-; high-risk group); and group 4 (n = 35; donor CMV-, recipient CMV-). RESULTS: Twenty-nine patients (14.3%) developed symptomatic CMV disease at 169 +/- 117 days after liver transplantation: group 1, 16.4% versus group 2, 7.3% versus group 3, 25.9% versus group 4, 0%. Of these patients, 5 also had invasive CMV on liver biopsy, which was performed owing to abnormal liver functions. All 29 patients were treated with intravenous ganciclovir. One patient died owing to disseminated CMV, whereas the remaining 28 patients responded to treatment. Interestingly, 8 patients, including 1 who had invasive CMV hepatitis, developed symptomatic CMV within 90 days of liver transplantation even while on prophylactic valganciclovir. CONCLUSION: Valganciclovir failed to provide adequate prophylaxis following liver transplantation in our patients. The overall rate of CMV in seropositive donors and/or recipients was 17%, and in the high-risk group was 26%. Further prospective studies with measurement of ganciclovir concentrations are needed to elucidate the reasons for this unexpected failure.

Adult↗
PubMed2005

A trial of valganciclovir prophylaxis for cytomegalovirus prevention in lung transplant recipients.

Cytomegalovirus (CMV) infection is common after lung transplantation. We performed a prospective trial of valganciclovir prophylaxis in lung recipients with outcomes compared to matched historical controls. The valganciclovir group (n = 40) (including D+/R- and R+ patients) was prospectively enrolled, and received oral valganciclovir 900 mg once daily for 12 weeks. Historical controls (n = 40) received 12 weeks of daily intravenous ganciclovir if D+/R- or 12 weeks of oral ganciclovir if R+. CMV viral load testing was done at two-week intervals until 6 months posttransplant. Baseline demographics and immunosuppression were comparable in the two groups. The incidence of CMV viremia was 16/40 (40.0%) in the valganciclovir arm versus 18/40 (45%) in the ganciclovir arm (p = NS). The incidence of symptomatic CMV disease was 8/40 (20%) versus 7/40 (17.5%), respectively (p = NS). In both groups viremia, while on prophylaxis, was uncommon (valganciclovir: 0/40 and ganciclovir: 2/40). Peak viral load and time to viremia were similar in the two arms. High rates of viremia and symptomatic disease occurred in the D+/R- patients after discontinuation of prophylaxis. Genotypic CMV sequence analysis demonstrated low rates of ganciclovir resistance in both groups. Valganciclovir prophylaxis had similar efficacy to either intravenous ganciclovir (D+/R- patients), or oral ganciclovir (R+ patients) in lung recipients.

Administration, Oral↗
PubMed1999

Single-dose pharmacokinetics of valganciclovir in HIV- and CMV-seropositive subjects.

As a result of the low oral bioavailability of ganciclovir, a prodrug was developed to improve the bioavailability of ganciclovir. This study was designed to investigate the fasting, single-dose pharmacokinetics as well as the absolute and relative bioavailability of a valine ester prodrug of ganciclovir, valganciclovir, as compared to oral and intravenous ganciclovir in asymptomatic HIV+ and CMV+ subjects. In this open-label, randomized, three-period crossover study, 18 subjects received, in random order, single oral doses of valganciclovir 360 mg and ganciclovir 1000 mg and an intravenous infusion of ganciclovir 5 mg/kg over 1 hour. Valganciclovir was rapidly and extensively hydrolyzed to ganciclovir, resulting in significantly greater bioavailability compared to 1000 mg oral ganciclovir (60.9% vs. 5.6%, respectively). Higher peak serum concentrations were reached earlier following valganciclovir (ganciclovir [2.98 +/- 0.77 micrograms/mL at 1.0 +/- 0.3 h]) than following oral ganciclovir (0.47 +/- 0.17 microgram/mL and 2.2 +/- 1.0 h). Mean total ganciclovir AUCs following oral ganciclovir (1000 mg) and 360 mg valganciclovir (3.8 +/- 1.2 and 10.8 +/- 1.9 micrograms-h/mL) were less than that following a standard 5 mg/kg intravenous infusion of ganciclovir (25.1 +/- 3.8 micrograms-h/mL). In summary, valganciclovir is a prodrug with a favorable safety profile with enhanced bioavailability and significantly higher serum concentrations of ganciclovir than following oral administration of ganciclovir itself.

Adult↗