Ganciclovir therapeutic drug monitoring in transplant recipients.

The Journal of antimicrobial chemotherapy 2021 Aug 12

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The use of (val)ganciclovir is complicated by toxicity, slow response to treatment and acquired resistance. To evaluate a routine therapeutic drug monitoring (TDM) programme for ganciclovir in a transplant patient population. An observational study was performed in transplant recipients from June 2018 to February 2020. Dose adjustments were advised by the TDM pharmacist as part of clinical care. For prophylaxis, a trough concentration (Cmin) of 1-2 mg/L and an AUC24h of >50 mg·h/L were aimed for. For treatment, a Cmin of 2-4 mg/L and an AUC24h of 80-120 mg·h/L were aimed for. Ninety-five solid organ and stem cell transplant patients were enrolled. Overall, 450 serum concentrations were measured; with a median of 3 (IQR = 2-6) per patient. The median Cmin and AUC24h in the treatment and prophylaxis groups were 2.0 mg/L and 90 mg·h/L and 0.9 mg/L and 67 mg·h/L, respectively. Significant intra- and inter-patient patient variability was observed. The majority of patients with an estimated glomerular filtration rate of more than 120 mL/min/1.73 m2 and patients on continuous veno-venous haemofiltration showed underexposure. The highest Cmin and AUC24h values were associated with the increase in liver function markers and decline in WBC count as compared with baseline. This study revealed that a standard weight and kidney function-based dosing regimen resulted in highly variable ganciclovir Cmin and under- and over-exposure were observed in patients on dialysis and in patients with increased renal function. Clearly there is a need to explore the impact of concentration-guided dose adjustments in a prospective study. © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Citation

Anne-Grete Märtson, Angela E Edwina, Johannes G M Burgerhof, Stefan P Berger, Anoek de Joode, Kevin Damman, Erik A M Verschuuren, Hans Blokzijl, Martijn Bakker, Lambert F Span, Tjip S van der Werf, Daan J Touw, Marieke G G Sturkenboom, Marjolein Knoester, Jan W C Alffenaar. Ganciclovir therapeutic drug monitoring in transplant recipients. The Journal of antimicrobial chemotherapy. 2021 Aug 12;76(9):2356-2363