Ganciclovir Pharmacokinetic Parameters Do Not Change When Extending Valganciclovir Cytomegalovirus Prophylaxis From 100 to 200 Days

Welker, H. A.; Farhan, Mahdi; Humar, Atul; Washington, Carla

doi:10.1097/tp.0b013e3182000042

Cited by 19 publications

(25 citation statements)

References 15 publications

(16 reference statements)

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“…Welker et al conducted a PK substudy (n = 120) from a multicentre double‐blind, randomised, placebo‐controlled trial. The clinical trial compared 100 days versus 200 days of 900‐mg ValGCV daily prophylaxis (Valcyte; F Hoffmann‐La Roche Ltd) in 326 CMV D+/R− kidney transplant recipients (Table ) .…”

Section: Resultsmentioning

confidence: 99%

“…These results suggest exposures between 40 and 50 μg·h/mL prevent CMV viraemia in this particular population (D+/R−), where the absolute risk of CMV disease is the highest . Interestingly, GCV AUC 0‐24 values below 40 μg·h/mL have been reported in two studies that investigated D+/R− SOT recipients, despite following the manufacturer's dosing algorithm . Furthermore, Padullés et al found 81.5% of SOT recipients (D+/R−, D+/R+, D−/R+, D‐/R−) did not reach GCV exposures between 40 and 50 μg·h/mL when following the manufacturer's dosing algorithm.…”

Section: Discussionmentioning

confidence: 96%

“…Current consensus recommendations for ValGCV and GCV dosing for patients with renal impairment include a standardised nomogram that assigns patients to one of five dosing groups based on their calculated creatinine clearance . However, despite receiving these recommended dose adjustments, GCV AUC 0‐24 vary in SOT recipients, particularly those with fluctuating renal function, potentially leading to reduced clinical efficacy of GCV prophylaxis …”

Section: Discussionmentioning

confidence: 99%

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Systematic review of ganciclovir pharmacodynamics during the prevention of cytomegalovirus infection in adult solid organ transplant recipients

Wong

Zuylen

Craig

et al. 2018

Reviews in Medical Virology

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Summary Human cytomegalovirus (CMV) represents the most common infection among recipients of solid organ transplants (SOTs). Previous meta‐analysis showed 0.8% of SOT recipients developed CMV disease whilst receiving valganciclovir (ValGCV) prophylaxis. However, the clinical utility of monitoring ganciclovir (GCV) blood concentrations is unclear. We systematically reviewed the association between GCV concentrations during prophylaxis and the incidence of CMV. MEDLINE and EMBASE databases were searched for studies between 1946 and 2018, where GCV pharmacokinetics and incidence of CMV viraemia or disease in SOT were available. Research designs included randomised trials, comparative, prospective cohort, retrospective, or case report studies. Only human adult studies were included, with English language restriction. The 11 studies that met the eligibility criteria included 610 participants receiving GCV or ValGCV prophylaxis. Quality assessment showed 2/4 randomised trials, 4/6 cohort studies, and 1/1 case report were of high quality. Despite dose adjustments for renal impairment, mean GCV exposures for patients were heterogeneous and ranged between 28 and 53.7 μg·h/mL across three randomised trials. The incidence of CMV infection and disease ranged from 0% to 50% and 0% to 3.1%, respectively, with follow up between 3 to 9 months. One study showed statistical power in determining relationship, where GCV exposure at 40 to 50 μg·h/mL in high‐risk SOT recipients was associated with a reduced risk of viraemia. Clinical monitoring for GCV exposure can be applied to high‐risk SOT recipients during ValGCV prophylaxis; however, further studies are needed to determine the utility of monitoring in all SOT recipients.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Systematic review of ganciclovir pharmacodynamics during the prevention of cytomegalovirus infection in adult solid organ transplant recipients

Wong

Zuylen

Craig

et al. 2018

Reviews in Medical Virology

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“…The average exposure at time of event was calculated taking the dosing history of the patient into account. The correlation analyses between individual ganciclovir AUC 0–24 and the occurrence of safety adverse events (yes/no) were performed by logistic regression, as described previously …”

Section: Methodsmentioning

confidence: 99%

“…The average exposure at time of event was calculated taking the dosing history of the patient into account. The correlation analyses between individual ganciclovir AUC 0 -24 and the occurrence of safety adverse events (yes/no) were performed by logistic regression, as described previously 2,28. RESULTSValganciclovir dosing algorithms for the prevention of CMV diseaseThe simulated median AUC 0-24 values, together with the fraction of patients within, below, and above the target range of 40-60 μg • hour/mL for each age group after dosing with valganciclovir are summarized inTable 2.…”

mentioning

confidence: 99%

Pediatric Dosing of Ganciclovir and Valganciclovir: How Model‐Based Simulations Can Prevent Underexposure and Potential Treatment Failure

Jorga¹,

Reigner

Chavanne

et al. 2018

CPT Pharmacom & Syst Pharma

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Intravenous ganciclovir and oral valganciclovir are effective in the prevention and treatment of pediatric cytomegalovirus ( CMV ) infection but various dosing regimens are used in medical practice. Population pharmacokinetic (PopPK) model‐based simulations were used to propose a new ganciclovir pediatric dosing algorithm for regulatory review and to evaluate the approved valganciclovir pediatric dosing algorithm against published dosing recommendations derived from quantitative approaches. Oral valganciclovir (mg = 7 × body surface area ( BSA ) × creatinine clearance according to the Schwarz formula (Cr CLS ) daily) and i.v. ganciclovir (mg = 3 × BSA × Cr CLS daily) are effective in reaching ganciclovir target exposure for the prevention of CMV (area under the concentration‐time curve ( AUC ) 0–24 40–60 μg ∙ hour/ mL ) in most pediatric patients across the full pediatric age range. In contrast, ganciclovir and valganciclovir dosing based on body weight, as commonly used in medical practice, leads to underexposure, particularly in younger pediatric patients. This example shows that model‐based dosing algorithms built on clinical pharmacology and implemented using good modeling practice can prevent underexposure and reduce the risk of treatment failure in pediatric patients.

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Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients

Hodson

Ladhani

Webster

et al. 2013

Cochrane Database of Systematic Reviews

121

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Ganciclovir Pharmacokinetic Parameters Do Not Change When Extending Valganciclovir Cytomegalovirus Prophylaxis From 100 to 200 Days

Cited by 19 publications

References 15 publications

Systematic review of ganciclovir pharmacodynamics during the prevention of cytomegalovirus infection in adult solid organ transplant recipients

Systematic review of ganciclovir pharmacodynamics during the prevention of cytomegalovirus infection in adult solid organ transplant recipients

Pediatric Dosing of Ganciclovir and Valganciclovir: How Model‐Based Simulations Can Prevent Underexposure and Potential Treatment Failure

Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients

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