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Background: This report presents the case of a patient with drug-resistant epilepsy. Despite treatment with 4 antiepileptic drugs, the patient experienced an increasing frequency of focal seizures, necessitating hospitalization, and continuous intravenous midazolam infusion., Methods: Cobicistat was introduced as a pharmacokinetic booster to decrease the metabolic clearance of midazolam, leading to increased exposure and an extended half-life., Results: Cobicistat boosting allowed the switch from intravenous to oral midazolam, and the patient was discharged on an oral midazolam regimen., Conclusions: Cobicistat can be effectively used to boost midazolam exposure pharmacokinetically in patients with drug-resistant epilepsy who require stable midazolam blood concentrations., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.)

Objectives: Infliximab is an antitumour necrosis factor agent used to treat inflammatory bowel disease (IBD). Measurement of infliximab trough concentrations (C-troughs) are used to optimize drug exposure and improve outcomes. Currently, enzyme-linked immunosorbent assays (ELISAs) are used predominantly for this purpose. Novel lateral flow immunoassays provide a rapid result., Methods: We collected 100 paired serum samples of adolescents and young adults with IBD, who were treated with infliximab maintenance infusions. C-troughs were measured with the Quantum Blue® lateral flow test (QB) with ELISA. Results were categorized as low-range (mean C-trough ≤5 µg/mL) or high-range (>5 µg/mL). A Bland-Altman plot was created with limits of clinical acceptability set at ≤2 µg/mL for low-range and ≤40% for high-range C-troughs. A concordance matrix was created to evaluate the C-trough-based clinical scenario (whether or not to escalate infliximab) using a cutoff value of 5 µg/mL., Results: Agreement between QB and ELISA was good (intraclass correlation coefficient: 0.85). In the low-range, 90% (95% confidence interval [CI]: 79-96) of measurements were within the limits of clinical acceptability. In the high-range this was 67% (95% CI: 53-79). QB provided higher results than ELISA. The concordance matrix showed 81% agreement (95% CI: 72-88, κ: 0.62)., Conclusions: Lateral flow- and ELISA-based infliximab C-trough measurements were in agreement. The swift establishment of infliximab C-troughs matters for patients experiencing increased disease activity. In the event of a low C-trough, prompt dose escalation can be initiated., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Preconditioning of donor livers before organ retrieval may improve organ quality after transplantation. We investigated whether preconditioning with metformin reduces preservation injury and improves hepatobiliary function in rat donor livers during ex situ normothermic machine perfusion (NMP) and after orthotopic liver transplantation., Methods: Lewis rats were administered metformin via oral gavage, after which a donor hepatectomy was performed followed by a standardized cold storage period of 4 hours. Graft assessment was performed using NMP via double perfusion of the hepatic artery and portal vein. In an additional experiment, rat donor livers preconditioned with metformin were stored on ice for 4 hours and transplanted to confirm postoperative liver function and survival. Data were analyzed and compared with sham-fed controls., Results: Graft assessment using NMP confirmed that preconditioning significantly improved ATP production, markers for hepatobiliary function (total bile production, biliary bilirubin, and bicarbonate), and significantly lowered levels of lactate, glucose, and apoptosis. After orthotopic liver transplantation, metformin preconditioning significantly reduced transaminase levels., Conclusions: Preconditioning with metformin lowers hepatobiliary injury and improves hepatobiliary function in an in situ and ex situ model of rat donor liver transplantation.

Objectives: 5-Aminosalicylic acid (5-ASA) is an important maintenance drug for patients with ulcerative colitis. A proportion of the ingested dose is excreted in the urine. Measuring 5-ASA and its metabolites in urine requires mass spectrometry, which is not widely available for this purpose. Urinary 5-ASA can be measured by colorimetry using the serum salicylic acid assay and is a surrogate marker of recent 5-ASA ingestion. We evaluated whether measuring 5-ASA in first morning voids or in random spot urine samples correctly identifies teenagers with poor adherence to oral 5-ASA., Methods: Teenagers who were prescribed a current regimen including >40 mg · kg · day of 5-ASA were invited to collect their spot urine with various time lapses since their last presumed 5-ASA ingestion. Classification of adherence was based on a composite method that included a patient-reported adherence scale and 6-thioguanine levels in erythrocytes., Results: Teenagers who were classified as "good adherers" had 66 of 69 (96%; 95% confidence interval 87%-99%) spot urine samples with detectable 5-ASA levels. "Poor adherers" had 30 of 45 (67%; 95% confidence interval 52%-79%) spot urine samples with undetectable 5-ASA levels. The "good adherers" with false-negative urine tests were on a once daily dosing regimen and had collected a spot urine sample shortly before the next dosage. Their first morning voids had detectable 5-ASA levels., Conclusions: Undetectable 5-ASA levels in the first morning void confirms short-term nonadherence to oral 5-ASA.