Pharmacokinetic and Pharmacodynamic Assessment of Oral Valganciclovir in the Treatment of Symptomatic Congenital Cytomegalovirus Disease

Kimberlin, David W.; Acosta, Edward P.; Sánchez, Pablo J.; Sood, Sunil K.; Agrawal, Vish; Homans, James; Jacobs, Richard F.; Lang, David J.; Romero, José R.; Griffin, Johanna A.; Cloud, Gretchen A.; Lakeman, Fred D.; Whitley, Richard J.

doi:10.1086/528376

Cited by 253 publications

(162 citation statements)

References 30 publications

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“…Administration of Ganciclovir or Valganciclovir should be initiated for neonatal disease early in infancy to have any meaningful use, if possible within the first 1 month of life. Rates of severe neutropenia are seen in up to two-thirds of infants treated with intravenous Ganciclovir [22][23][24][25][26].…”

Section: Discussionmentioning

confidence: 99%

Childhood Cytomegalovirus Infection: Case Series and Literature Review

Alemayehu¹,

Abebe²,

Hailu³

2017

Virol Mycol

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Section: Discussionmentioning

confidence: 99%

Childhood Cytomegalovirus Infection: Case Series and Literature Review

Alemayehu¹,

Abebe²,

Hailu³

2017

Virol Mycol

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“…Other authors have not been able to correlate drug levels with clinical or virological efficacy [6,9].…”

Section: Discussionmentioning

confidence: 99%

“…However, owing to the firstorder kinetics exhibited by GCV, AUC has been shown to correlate with both peak drug concentration (C max ) and trough levels, which are taken for TDM, suggesting that these parameters may be useful indicators of AUC [8]. Lower trough levels (<0.6 mg/L) have been associated with a higher incidence of disease progression in a study of CMV retinitis in adult human immunodeficiency virus (HIV) patients, although other authors have not been able to correlate drug levels with clinical or virological efficacy [5,6,9]. Other factors may also potentially affect treatment efficacy, including virus genotype, host immune responses and levels of GCV-triphosphate actually achieved in target body tissues; some of these parameters may be anticipated to vary significantly with age.…”

Section: Page 4 Of 19mentioning

confidence: 99%

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Ganciclovir treatment in children: evidence of subtherapeutic levels

Luck

Lovering

Griffiths

2011

International Journal of Antimicrobial Agents

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Ganciclovir (GCV) is used to treat babies and older children with cytomegalovirusrelated disease. Treatment courses are generally derived from adult studies and there are few data relating to the pharmacokinetics of GCV in children. In adults, low trough GCV levels have been associated with treatment failure and virological resistance. Data regarding suitable drug levels for use in therapeutic drug monitoring (TDM) in the paediatric age group do not currently exist. In this study, anonymised data for all GCV levels sent to the UK Antibiotic Reference Laboratory from 1 November 1999 to 31 March 2007 were reviewed and analysed by age group. In total, 339 specimens were received from 129 patients; 192 specimens were from patients aged <18 years. There were significantly more trough GCV levels <0.5 mg/L in those aged <6 months and 6-12 months compared with adults (64.8% and 53.9%, respectively, vs. 15.9%; P < 0.001). Those aged 5-18 years also had significantly more trough samples with levels <0.5 mg/L (80.0% vs. 15.9%; P < 0.001). There was a significant difference between median peak GCV levels in those aged <6 months and adults (4.8 mg/L vs. 5.7 mg/L, respectively; P = 0.047). In conclusion, GCV levels associated with treatment failure and considered subtherapeutic in adult patients were observed more often in specimens from paediatric patients. These lower levels may have implications for dosing in the paediatric age group, particularly during periods of rapid change in renal function such as the neonatal period.Clinicians should be aware of the relatively low drug exposure noted in this study and consider TDM and increasing drug dose where virological response is poor.

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“…Ganciclovir inhibits CMV replication by inactivation of viral DNA polymerase and is used in the treatment of CMV infections in immunecompromised patients. 26 In newborns, ganciclovir has been shown to decrease virus shedding in urine and the medication has been shown to be effective in reducing hearing deficits in infants with congenital CMV infection. The medication has been shown to decrease viral loads and is tolerated in preterm infants with congenital CMV infection.…”

Section: Treatmentmentioning

confidence: 99%

CMV Infection in Pregnancy

Goh¹,

Sauvage²

2010

Donald School Journal of Ultrasound in Obstetrics and Gynecology

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Cytomegalovirus (CMV) is a common and serious congenital infection affecting between 1 to 4% of newborns. Congenital infections can occur after both primary and recurrent maternal infections and are the major cause of childhood deafness, visual impairment, mental retardation and motor spastic or convulsive syndromes. Ultrasound findings including IUGR, ventriculomegaly, brain and hepatic and bowel calcifications, polyhydramnios, hydrops fetalis and pleural effusions are helpful and can aid in the prenatal diagnosis and followup of congenital CMV infection. CMV hyperimmunoglobulin is safe, and may be an effective treatment to minimize the morbidity and mortality of fetal CMV disease. There is ongoing research into the development of an effective vaccine for the prevention of CMV infection during pregnancy. Objectives Understand why CMV is an important cause of congenital injections Understand the role of ultrasound in the diagnosis of intrauterine CMV infections Understand the possible treatment options for a fetus infected with CMV

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Pharmacokinetic and Pharmacodynamic Assessment of Oral Valganciclovir in the Treatment of Symptomatic Congenital Cytomegalovirus Disease

Cited by 253 publications

References 30 publications

Childhood Cytomegalovirus Infection: Case Series and Literature Review

Childhood Cytomegalovirus Infection: Case Series and Literature Review

Ganciclovir treatment in children: evidence of subtherapeutic levels

CMV Infection in Pregnancy

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