The aim of this prospective study was to evaluate the pharmacokinetics of ganciclovir in lung transplant recipients, to explore its covariates, and to propose an individualized dosing regimen. Ganciclovir was administered according to the protocol in a standardized intravenous dose of 5 mg/kg twice daily. Serum ganciclovir concentrations were monitored as a trough and at 3 and 5 h after dosing. Individual ganciclovir pharmacokinetic parameters were calculated in a two-compartmental pharmacokinetic model, while regression models were used to explore the covariates. Optimal loading and maintenance doses were calculated for each patient. In lung transplant recipients (n = 40), the median (IQR) ganciclovir total volume of distribution and clearance values were 0.65 (0.52–0.73) L/kg and 0.088 (0.059–0.118) L/h/kg, respectively. We observed medium-to-high inter-individual but negligible intra-individual variability in ganciclovir pharmacokinetics. The volume of distribution of ganciclovir was best predicted by height, while clearance was predicted by glomerular filtration rate. Bodyweight-normalized clearance was significantly higher in patients with cystic fibrosis, while distribution half-life was reduced in this subgroup. On the basis of the observed relationships, practical nomograms for individualized ganciclovir dosing were proposed. The dosing of ganciclovir in patients with cystic fibrosis requires special caution, as their daily maintenance dose should be increased by approximately 50%.
One of the officially approved medications for the treatment of the pandemic disease COVID-19, caused by the SARS-CoV-2 virus, is remdesivir. This antiviral molecule is a prodrug that is metabolized into its active form (an ATP analogue). Because of its hepatotoxicity and nephrotoxicity, it is necessary to monitor the serum concentrations of remdesivir. For the therapeutic drug monitoring of remdesivir, a method using liquid chromatography with tandem mass spectrometry (LC-MS/MS) in positive electrospray ionization mode was developed. Mass detection was done via triple quadrupole in the Multiple reaction monitoring mode. Separation was done on Zorbax C18 column at 35 °C in mobile phase gradient and flow 0.4 mL min–1 (A – 0.1% formic acid in water, B – 0.1% formic acid in 95% acetonitrile). Time of analysis was 4 minutes. LC-MS/MS method was successfully validated. Calibration was done in blood serum and plasma and it was linear in the range of tested concentrations (0–1000 ng mL–1). Samples were prepared by protein precipitation. The method was used to measure remdesivir concentration in a patient with SARS-CoV-2 infection. The measured concentration 60 minutes after remdesivir application was 175±15 ng mL–1.
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