Ganciclovir treatment in children: evidence of subtherapeutic levels

Luck, Suzanne; Lovering, Andrew; Griffiths, Paul

doi:10.1016/j.ijantimicag.2010.11.033

Cited by 33 publications

(27 citation statements)

References 19 publications

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“…or prevention (q.d.) of CMV . Nevertheless, recent publications have challenged the valganciclovir pediatric dosing algorithm based on BSA/CrCLS, and simulations have suggested that a simple BW‐based dosing regimen of 14–16 mg/kg valganciclovir b.i.d .…”

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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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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“…There have been very few TDM data of ganciclovir therapy in extremely premature infants [4]. The response to therapy with ganciclovir has been influenced by the interindividual pharmacokinetic variability.…”

Section: Discussionmentioning

confidence: 99%

“…The response to therapy with ganciclovir has been influenced by the interindividual pharmacokinetic variability. Thus, low plasma levels of ganciclovir are associated with therapy failure and also predispose the virus to drug resistance, although optimal therapeutic drug levels have not been well established [4]. Plasma ganciclovir trough levels below 0.6 mg/L are associated with therapy failure during the intravenous ganciclovir administration for CMV retinitis [5].…”

Section: Discussionmentioning

confidence: 99%

“…Plasma ganciclovir trough levels below 0.6 mg/L are associated with therapy failure during the intravenous ganciclovir administration for CMV retinitis [5]. Based on existing data and concerns regarding under-treatment, a trough level of 0.5–1.0 mg/L may be optimal [4]. In our patients, we started ganciclovir therapy at 5 mg/kg per dose every 12 h. The ganciclovir peak level sufficiently increased; therefore, a ganciclovir dose of 5 mg/kg per dose appeared to be optimal.…”

Section: Discussionmentioning

confidence: 99%

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Therapeutic drug monitoring of ganciclovir for postnatal cytomegalovirus infection in an extremely low birth weight infant: a case report

et al. 2016

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BackgroundGanciclovir is a therapeutic choice for extremely premature infants with severe postnatal cytomegalovirus disease, but little is known about its optimal dose size and dosing interval for them.Case presentationWe treated an extremely premature female infant with postnatal cytomegalovirus infection with intravenous administration of ganciclovir since 49 days of life (postmenstrual age of 31 weeks). After ganciclovir treatment was initiated at a dose of 5 mg/kg every 12 h, cytomegalovirus loads in the peripheral blood were markedly decreased. However, since plasma ganciclovir trough level was too high, the interval was extended to every 24 h. Subsequently, the trough level and the estimated 12-h area under the concentration–time curve (AUC0–12) were decreased from 3.5 mg/L to 0.3 mg/L and 53.9 mg · h/L to 19.2 mg · h/L, respectively, resulting in an exacerbation of viremia and clinical condition. Adjustment of dosing interval from 24 h to 12 h led to a peak level of 4.2 mg/L, trough level of 1.1 mg/L, and AUC0–12 of 31.8 mg · h/L, resulting in a marked suppression of viral load.ConclusionsMonitoring the therapeutic drug levels and cytomegalovirus loads is useful in obtaining a proper treatment effect and preventing overdosage during ganciclovir therapy in premature infants with postnatal cytomegalovirus infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12887-016-0683-x) contains supplementary material, which is available to authorized users.

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“…The problem with this approach was highlighted by Veniza et al [142], who showed that out of eight patients with measured ganciclovir concentrations (following oral valganciclovir administration) which exceeded the in vitro IC50 for Epstein Barr Virus (EBV), four of them did not experience viral suppression. This hints at the problem outlined by Luck et al that the target circulating concentration for ganciclovir is often unknown, and further understanding of PKPD relationships is required [143].…”

Section: Infectious Diseasesmentioning

confidence: 99%

Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology

Barker

Germovsek²,

Hoare³

et al. 2014

Advanced Drug Delivery Reviews

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Pharmacokinetic/pharmacodynamic (PKPD) modelling is used to describe and quantify dose–concentration–effect relationships. Within paediatric studies in infectious diseases and immunology these methods are often applied to developing guidance on appropriate dosing. In this paper, an introduction to the field of PKPD modelling is given, followed by a review of the PKPD studies that have been undertaken in paediatric infectious diseases and immunology. The main focus is on identifying the methodological approaches used to define the PKPD relationship in these studies. The major findings were that most studies of infectious diseases have developed a PK model and then used simulations to define a dose recommendation based on a pre-defined PD target, which may have been defined in adults or in vitro. For immunological studies much of the modelling has focused on either PK or PD, and since multiple drugs are usually used, delineating the relative contributions of each is challenging. The use of dynamical modelling of in vitro antibacterial studies, and paediatric HIV mechanistic PD models linked with the PK of all drugs, are emerging methods that should enhance PKPD-based recommendations in the future.

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Ganciclovir treatment in children: evidence of subtherapeutic levels

Cited by 33 publications

References 19 publications

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

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

Therapeutic drug monitoring of ganciclovir for postnatal cytomegalovirus infection in an extremely low birth weight infant: a case report

Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology

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