Monitoring plasma levels of ganciclovir in AIDS patients receiving oral ganciclovir as maintenance therapy for CMV retinitis

Piketty, Christophe; Bardin, Christophe; Gilquin, Jacques; Gairard, A.; Kazatchkine, Michel D.; Chast, François

doi:10.1046/j.1469-0691.2000.00014.x

Cited by 34 publications

(22 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…GCV levels were defined as therapeutic (Ͼ0.6 mg/liter), subtherapeutic (Յ0.6 mg/liter), or severely deficient (Ͻ0.3 mg/liter) (7,8). Renal function (eGFR, C-G, and mCCl) was assessed whenever GCV levels were measured.…”

mentioning

confidence: 99%

“…The minimum GCV trough concentration required to prevent CMV viremia and disease are not well defined. Based on previous studies largely assessing CMV disease prevention in HIV-infected patients, we classified levels of Յ0.6 mg/liter as subtherapeutic (8). For non-HIV immunosuppressed populations, such as SOT recipients, Erice et al (13) found that patients who did not have CMV disease had mean GCV trough levels of 0.7 g/ml, compared with 0.43 g/ml in those with progressive CMV.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Electronic Estimations of Renal Function Are Inaccurate in Solid-Organ Transplant Recipients and Can Result in Significant Underdosing of Prophylactic Valganciclovir

Trevillyan

Angus

Shelton

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

e In a prospective study of solid-organ transplant recipients (n ‫؍‬ 22; 15 hepatic and 7 renal) receiving valganciclovir for cytomegalovirus (CMV) prophylaxis, electronic estimation of glomerular filtration rate (eGFR) underestimated the true GFR (24-h urine creatinine clearance) by >20% in 14/22 (63.6%). Its use was associated with inappropriate underdosing of valganciclovir, while the Cockroft-Gault equation was accurate in 21/22 patients (95.4%). Subtherapeutic ganciclovir levels (<0.6 mg/liter) were common, occurring in 10/22 patients (45.4%); 7 had severely deficient levels (<0.3 mg/liter).

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Electronic Estimations of Renal Function Are Inaccurate in Solid-Organ Transplant Recipients and Can Result in Significant Underdosing of Prophylactic Valganciclovir

Trevillyan

Angus

Shelton

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Prophylactic oral dosing of GCV has been associated with GCV resistance and possible treatment failure, suspected to be due to the low serum drug levels achieved, and trough levels >0.6 mg/L have therefore been proposed by some authors as being optimal [5,13,14]. There is a risk that the low concentrations seen in the paediatric population may likewise select for resistance and lead to treatment failure.…”

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%

See 1 more Smart Citation

Ganciclovir treatment in children: evidence of subtherapeutic levels

Luck

Lovering

Griffiths

2011

International Journal of Antimicrobial Agents

View full text Add to dashboard Cite

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.

show abstract

A simple and simultaneous determination of acyclovir and ganciclovir in human plasma by high‐performance liquid chromatography

Teshima

Otsubo

Yoshida

et al. 2003

Biomedical Chromatography

View full text Add to dashboard Cite

A simple high-performance liquid chromatographic method was developed for the simultaneous determination of the therapeutic levels of acyclovir and ganciclovir in human plasma. After precipitation of plasma proteins with 6% perchloric acid, acyclovir and ganciclovir were simultaneously determined by reversed-phase chromatography with spectophotometric detection at 254 nm. The peak heights for acyclovir and ganciclovir were linearly related to their concentrations ranging from 0.063 to 2.080 micro g/mL. The recovery was 100.48-102.84% for acyclovir and 99.26-103.07% for ganciclovir. The intra- and inter-day relative standard deviation values were in the range 0.186-8.703% for acyclovir and 0.137-6.424% for ganciclovir. The detection limits for both compounds were 0.01 micro g/mL determined as the signal-to-noise ratio of 3. The present method is applicable to therapeutic monitoring during antiviral medication.

show abstract

Monitoring plasma levels of ganciclovir in AIDS patients receiving oral ganciclovir as maintenance therapy for CMV retinitis

Abstract: Patients exhibiting trough plasma levels of ganciclovir below 0.6 mg/L may be at higher risk of progression than patients who exhibited levels above 0.6 mg/L.

Cited by 34 publications

References 18 publications

Electronic Estimations of Renal Function Are Inaccurate in Solid-Organ Transplant Recipients and Can Result in Significant Underdosing of Prophylactic Valganciclovir

Electronic Estimations of Renal Function Are Inaccurate in Solid-Organ Transplant Recipients and Can Result in Significant Underdosing of Prophylactic Valganciclovir

Ganciclovir treatment in children: evidence of subtherapeutic levels

A simple and simultaneous determination of acyclovir and ganciclovir in human plasma by high‐performance liquid chromatography

Contact Info

Product

Resources

About