Contribution of Population Pharmacokinetics to Dose Optimization of Ganciclovir-Valganciclovir in Solid-Organ Transplant Patients

Abstract

Treatment of solid-organ transplant (SOT) patients with ganciclovir (GCV)-valganciclovir (VGCV

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

“…Padullés et al performed a two‐arm, randomised, open‐label, single centre trial in 53 SOT recipients administered with ValGCV (Valcyte; F Hoffmann‐La Roche Ltd) and intravenous GCV (Cymevene; F Hoffman‐La Roche Ltd) for prophylaxis or treatment (Table ). Group A (n = 27) followed the manufacturer's recommended dose adjustments according to creatinine clearance calculated using the C‐G formula.…”

“…The majority (10/11) of included studies lacked statistical power to determine the relationship between CMV detection and GCV concentrations. This is likely explained by the limited sample size and low incidence (0‐6.1%) of CMV infection during prophylaxis . One small (n = 22) study reported an unusually high incidence (50%) of CMV viraemia; however, this was not significantly correlated with trough GCV concentration .…”

“…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. This suggests suboptimal GCV dosing occurs in the presence of apparently appropriate GCV treatment.…”

“…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 …”

“…[10][11][12]49,50 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. 27,32,34 At present, GCV and ValGCV dosing decisions are not routinely informed by use of a therapeutic range. The target cut-offs for C min vary across different laboratories and range between 0.06 and 2.5 μg/mL in human organ and tissue transplant studies.…”