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J.H. and T.K. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis, and they participated in drafting of the article, statistical analysis, and data visualization.

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%.

This pilot prospective study verified the hypothesis that use of computer-assisted therapeutic drug monitoring of aminoglycosides by pharmacists leads to better safety therapeutic outcomes and cost avoidance than only concentration measurement and dose adjustments based on a physician’s experience. Two groups of patients were enrolled according to the technique of monitoring. Patients (Group 1, n=52) underwent monitoring by a pharmacist using pharmacokinetic software. In a control group (Group 2, n=11), plasma levels were measured but not interpreted by the pharmacist, only by physicians. No statistically significant differences were found between the groups in factors influenced by therapy. However, the results are not statistically significant but a comparison of the groups showed a clear trend towards safety and cost avoidance, thus supporting therapeutic drug monitoring. Safety limits were achieved in 76 % and 63 % of cases in Groups 1 and 2, respectively. More patients achieved both concentrations (peak and trough) with falling eGFR in Group 1. In present pilot study, the pharmacist improved the care of patients on aminoglycoside therapy. A larger study is needed to demonstrate statistically significantly improved safety and cost avoidance of aminoglycoside therapy monitoring by the pharmacist using pharmacokinetic software.

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Peritonitis is a limiting complication of peritoneal dialysis, which is treated by intraperitoneal administration of antibiotics. Various dosing strategies are recommended for intraperitoneally administered vancomycin, which leads to large differences in intraperitoneal vancomycin exposure. Based on data from therapeutic drug monitoring, we developed the first-ever population pharmacokinetic model for intraperitoneally administered vancomycin to evaluate intraperitoneal and plasma exposure after dosing schedules recommended by the International Society for Peritoneal Dialysis. According to our model, currently recommended dosing schedules lead to possible underdosing of a large proportion of patients. To prevent this, we suggest avoiding intermittent intraperitoneal vancomycin administration, and for the continuous dosing regimen, we suggest a loading dose of 20 mg/kg followed by maintenance doses of 50 mg/L in each dwell to improve the intraperitoneal exposure. Vancomycin plasma level measurement on the fifth day of treatment with subsequent dose adjustment would prevent it from reaching toxic levels in the few patients who are susceptible to overdose.

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