Effects of rifampin coadministration on the pharmacokinetics of digoxin: a real-world data approach.

Digoxin, a cardiac glycoside, is commonly prescribed to treat heart failure and atrial fibrillation. Because digoxin acts as a substrate of P-glycoprotein (P-gp), its blood concentration may be reduced by P-gp inducers such as rifampin. To assess the real-world implications of this drug-drug interaction, a retrospective analysis was carried out on the Clinical Data Warehouse at Seoul National University Hospital between 2012 and 2017. Eleven patients who received both digoxin and rifampin with satisfying the inclusion/exclusion criteria were identified. The Ctrough values of digoxin monotherapy were compared to those of the combination therapy with rifampin. Results demonstrated that the systemic exposure of orally administered digoxin decreased by 40% with the concurrent use of rifampin. Clinicians should be aware of potential drug interactions between digoxin and rifampin, as adjustments to digoxin dosage might be necessary for patients receiving rifampin or other P-gp inducer drugs.

Pharmacodynamic and Pharmacokinetic Drug Interactions between Fexuprazan, a Novel Potassium-Competitive Inhibitor, and Aspirin, in Healthy Subjects.

Acid-reducing agents are commonly used for the prevention of aspirin-induced gastrointestinal complications such as peptic ulcers. As a novel potassium-competitive acid blocker, fexuprazan is expected to prevent aspirin-induced gastrointestinal complications. This randomized, open-label study aimed to evaluate the pharmacodynamic and pharmacokinetic interactions between aspirin and fexuprazan in healthy Koreans. Subjects randomized to the aspirin group received 500 mg aspirin in combination with 80 mg fexuprazan. For the fexuprazan group, fexuprazan 80 mg was administered alone and then in combination with aspirin 500 mg. Platelet aggregation inhibited by aspirin and the pharmacokinetic parameters of aspirin and fexuprazan were compared between monotherapy and combination therapy. A total of 22 subjects completed the study. The platelet aggregation-inhibitory activity and systemic exposure to aspirin were not significantly affected by fexuprazan coadministration. The systemic exposure of fexuprazan was decreased up to 20% by aspirin coadministration, which was not regarded as clinically meaningful considering the previously reported exposure-response relationship. In conclusion, there were no clinically relevant pharmacodynamic or pharmacokinetic interactions between aspirin and fexuprazan. This finding suggests the potential of fexuprazan for the prevention of aspirin-induced gastrointestinal complications, serving as a baseline for optimizing its therapeutic application with aspirin.

Considerations for clinical evaluation of the effects of bariatric surgery on the pharmacokinetics of orally administered drugs.

Obesity has been a growing worldwide concern, and surgical intervention including bariatric surgery is considered as one of the options for treatment. However, there still is controversy over the change in pharmacokinetics (PKs) of drugs after the surgery. To investigate the potential covariates that can influence the area under the curve (AUC) and maximum plasma concentration (Cmax), the design of previous studies was reviewed based on pre-determined eligibility criteria. Each study calculated the ratios of the AUC and Cmax before and after bariatric surgery. These studies investigated whether the PK parameters were affected by the time after the surgery or by the type of control group. The ratio of the AUC calculated in the early and late follow-up period was similar across Roux-en Y gastric bypass patients. No significant difference in the PK parameters was found between the pre-surgical patients and matched healthy subjects. However, certain control groups could be preferable depending on the purpose of the clinical trial. Although Cmax was inconsistent compared to the AUC, insufficient sampling of the time points may have caused such an inconsistency. This is the first article exploring the appropriate methodology in designing clinical studies for changes in the PK characteristics of orally administered drugs in patients with bariatric surgery.