We report a case of a man with COVID-19 who developed acute hepatotoxicity related to remdesivir with probable interaction of P-glycoprotein (P-gp) inhibitors. Until further details on this interaction become available, we recommend physicians to be cautious with the prescription of P-gp inhibitors in patients receiving remdesivir therapy.

Objectives: To describe the population pharmacokinetics and protein-binding characteristics of unbound ceftriaxone administered as continuous or intermittent infusion. Additionally, to determine the optimal dosing regimen in critically ill patients. Methods: A pharmacokinetic study was performed in the ICU of a tertiary teaching hospital. Patients were treated with ceftriaxone as continuous or intermittent infusion. A population pharmacokinetic model was developed with non-linear mixed-effects analysis. Subsequently, the PTA of a 100% T-> MIC was assessed for influential patient characteristics using Monte Carlo simulation. Results: Fifty-five patients were included. The pharmacokinetics of ceftriaxone was best described by a one-compartment model with non-linear saturable protein binding including the following covariates: body weight, estimated CLCR, serum albumin concentration and mode of administration. For pathogens with an MIC of 1 mg/L, the simulation demonstrated that intermittent infusion of 2 g/24 h only resulted in a >= 90% PTA in patients with a reduced CLCR (0-60 mL/min). Intermittent infusion of 2 g/12 h led to sufficient exposure if CLCR was 0-90 mL/min and continuous infusion of 2 g/24 h led to a >= 90% PTA in all simulations (CLCR 0-180 mL/min). Conclusions: In the critically ill, the clearance of unbound ceftriaxone is closely related to CLCR. Furthermore, ceftriaxone protein binding is saturable, variable and dependent on serum albumin concentration. Intermittent dosing of 2 g/24 h ceftriaxone leads to subtherapeutic exposure in patients with a normal or increased CLCR. Treating these patients with continuous infusion of 2 g/24 h is more effective than an intermittent dosing regimen of 2 g/12 h.

The objective of this study was to describe the population pharmacokinetics of remdesivir and GS-441524 in hospitalized coronavirus disease 2019 (COVID-19) patients. A prospective observational pharmacokinetic study was performed in non-critically ill hospitalized COVID-19 patients with hypoxemia.

Introduction Hypokalemia is a potentially life-threatening adverse event of flucloxacillin with unknown incidence. The risk of flucloxacillin-induced hypokalemia has recently been suggested to be increased among females compared to males. The aim of this study is to describe the incidence and to determine the influence of sex and other risk factors on flucloxacillin-induced hypokalemia. Methods A retrospective single-centre cohort study was performed. Patients treated with intravenous flucloxacillin for >24 hours between January 2017 and October 2020, a baseline potassium level of ≥3.5 mmol/L and potassium measurement during treatment were included. The primary endpoint was incidence of hypokalemia defined as the percentage of patients with a potassium measurement <3.5 mmol/L during flucloxacillin treatment. Logistic regression modelling was used to establish risk factors for hypokalemia. Results 835 patients were included, 58.2% male and median age 71.0 year [IQR 61.0-81.0]. The incidence of hypokalemia was 23.7% (28.4% in females vs 20.4% in males). A dose-dependent relation between sex and the incidence of hypokalemia was found. The risk of hypokalemia was 4.41 (95% CI 1.47-13.24) times higher in females compared to males when receiving a flucloxacillin dose of >8 g/24 hours. No sex differences were found for lower daily doses. Other risk factors for hypokalemia were older age, concomitant antibiotic use, lower bodyweight, lower baseline plasma potassium concentration and longer treatment duration. Conclusion Hypokalemia is a frequent complication in patients treated with intravenous flucloxacillin. Females receiving >8 g intravenous flucloxacillin per day are more prone to develop hypokalemia compared to males.

Background and objectives: Posaconazole is used as prophylaxis of invasive fungal disease in immune-compromised haematological patients with prolonged neutropenia after intensive chemotherapy. During routine therapeutic drug monitoring of posaconazole, we repeatedly observed low posaconazole serum concentrations in patients that were concomitantly treated with flucloxacillin. A possible interaction between flucloxacillin and posaconazole was explored in this case series. Patients and methods: Posaconazole trough serum concentrations during and before/after flucloxacillin treatment were collected from 10 patients. Results: With a median concentration of 0.5 mg/L (IQR 0.3–0.6), the posaconazole trough serum concentration decreased by 47% during flucloxacillin treatment compared with the concentration before/after flucloxacillin treatment (0.9 mg/L, IQR 0.6–1.3). As a result, the posaconazole target trough concentration of ≥0.7 mg/L was only achieved in five out of nine patients during flucloxacillin treatment. Conclusions: Careful monitoring of posaconazole serum trough concentrations is recommended when concomitant use of flucloxacillin cannot be avoided.