Results From a Randomized, Open-Label, Crossover Study Evaluating the Effect of the Aldosterone Synthase Inhibitor Baxdrostat on the Pharmacokinetics of Metformin in Healthy Human Subjects.

BACKGROUND: Due to the high comorbidity of diabetes and hypertension, co-administration of metformin with anti-hypertensive drugs is likely. Baxdrostat is an aldosterone synthase inhibitor in development for the potential treatment of hypertension. In vitro data indicated that baxdrostat inhibits the multidrug and toxin extrusion 1 (MATE1) and MATE2-K renal transporters. Metformin is a MATE substrate, so this study assessed potential effects of baxdrostat on the pharmacokinetics of metformin. METHODS: Twenty-seven healthy volunteers received 1000 mg metformin alone and 1000 mg metformin in the presence of 10 mg baxdrostat in a randomized, crossover manner. Each treatment was separated by 10 or more days. Blood and urine samples were collected over a 3-day period after each treatment to measure plasma and urine concentrations of metformin. Safety was assessed by adverse events (AEs), physical examinations, electrocardiograms, vital signs, and clinical laboratory evaluations. RESULTS: There were no deaths, serious AEs, discontinuations due to treatment-emergent AEs, or noteworthy increases in AEs with either treatment, indicating that metformin and baxdrostat were well-tolerated when co-administered. Baxdrostat did not significantly affect plasma concentrations or renal clearance of metformin. CONCLUSION: The results of this study suggest that diabetic patients with hypertension receiving both metformin and baxdrostat are unlikely to require dose adjustment. REGISTRATION: ClinicalTrials.gov identifier no. NCT05526690.

Medications in COVID-19 patients: summarizing the current literature from an orthopaedic perspective.

PURPOSE: The review aims to provide a summary of the current literature regarding common medications prescribed in orthopaedic surgery and their potential implications in COVID-19 patients. METHODS: A systematic review was performed using the PRISMA guidelines. All clinical studies, reviews, consensus and guidelines related to the above medications and COVID-19 were included. RESULTS: A total of 18 articles were included. The use of analgesia, anti-inflammatories, steroids, anticoagulants, antibiotics, vitamin B, vitamin C and vitamin D and their potential impact on COVID-19 patients were reported. CONCLUSION: Eight main recommendations were derived from the review. Firstly, paracetamol remains the first line of analgesia and antipyretic. Secondly, there is no need to avoid NSAIDs for COVID-19 patients. Thirdly, opioids have the potential for immunosuppression in addition to respiratory depression and, therefore, should be prescribed with care in COVID-19 patients. Fourthly, patients with conditions where steroids are proven to be efficacious can continue to receive their steroids; otherwise, systemic steroids are not recommended for COVID-19 patients. Fifthly, orthopaedic surgeons following up on COVID-19 patients who are using steroids should continue to follow them up for possible avascular necrosis. Sixthly, whenever possible, oral anticoagulation should be converted to parental heparin. Seventhly, common orthopaedic antibiotics including penicillin and clindamycin are safe to continue for COVID-19 patients. However, for COVID-19 patients, the antibiotics can potentially be switched to macrolides and tetracyclines if the organisms are sensitive. Lastly, prescription for vitamins B, C and D should continue as per usual clinical practice.