Rituximab is used for several indications including primary glomerulopathies; however, the optimal schedule in those diseases remains to be established. The aim of this study is to characterize rituximab pharmacokinetics in a population affected with glomerular diseases. A single-center, open-labelled, uncontrolled clinical trial was performed including adults affected by glomerular diseases who required rituximab (NEFRTX, EudraCT: 2020-000484-23). Patients received 1g or 0.5g of rituximab on day 1 (and 14 in some cases); blood and urine samples were collected. Rituximab and anti-rituximab concentrations were measured and the gene encoding the neonatal fragment crystallizable receptor (FcRn) was characterized. Win-Nonlin 1.1, was used for pharamacokinetic analysis. Thirty-five cases (30 patients) were included. Pharmacokinetic parameters (mean ± standard deviation): maximum plasma concentration 179.4±71.8µg/ml, volume of distribution 78.9±31.4ml/kg, clearance 0.30±0.27ml/h/kg, half-life (t1/2) 11.6±5.8d, elimination rate constant 0.0036±0.0030h⁻¹, area under the curve 117,756.1±88,228.1µg·h/ml. Anti-rituximab was detected on d1 in 3(8.6%) cases, they were negative by d28. No infusion reactions occurred. Rituximab t1/2 was characterized by the formula: t1/2=A-B·Log (Proteinuria)+C·Albuminemia; where A=515.0 (128.8, 901.3), B=182.1 (-108.6, -35.4), C=39.5 (-10.9, 89.9). There were differences in rituximab t1/2 depending on the presence of 24-hours proteinuria>2.4 g/24h (p<0.001), early treatment (p=0.008), diagnosis (p=0.025) and IgG<650 mg/dL (p=0.048). Our study confirms that albuminemia and especially proteinuria affect rituximab t1/2 and drug exposure in patients with primary glomerulopathies. Patients affected by membranous nephropathy and/or nephrotic syndrome and/or proteinuria >2.4 g/24h and/or IgG <650 mg/dl could need more frequent dosing. Further research is needed to establish an optimal dosing strategy in this population.

Aim Several cases of ertapenem-related neurotoxicity has been published in the current literature. However, studies evaluating the ertapenem blood concentration as a risk of these adverse events are scarce. We aimed to evaluate the relationship between the ertapenem concentration and the risk of neurological toxicity. Methods Retrospective study, including patients who underwent ertapenem treatment between october 2019 and february 2021. We excluded critical patients and those whose blood sample were not properly took in order to analyze ertapenem trough concentration. We also excluded patients whose clinical follow-up was not properly realized for the entire period of ertapenem treatment. The main outcome was the presence of any suspicious neurological side effect owing to ertapenem administration and its relationship with the plasma concentration. Secondary outcomes were to identify other clinical and analytical data contributing to a higher risk of neurotoxicity. Results Cohort was initially composed by 158 individuals. For the final analysis we evaluated 102 patients, reporting a neurological alteration in 13/102 (12.7%). Mean ertapenem trough plasma concentration was significantly higher in patients showing neurotoxicity in comparison with those who did not (37.8 mcg ml-1 SD±35.7 vs 14.6 mcg ml-1 SD±15.2; p=0.002). In multivariable logistic regression analysis, ertapenem plasma concentration (OR= 1.07; p=0.006), a moderate renal insuficiency (OR= 9.2; p=0.02) and a history of previous neurologic disease (OR=9.9;p=0.02) were identified as risk factors of neurological alteration during ertapenem treatment. Conclusions Identifying properly patients who may accumulate the antibiotic by determining their plasma levels could be helpful to minimize the risk of neurotoxicity.