Effect of haemodialysis on the pharmacokinetics and pharmacodynamics of evogliptin

Abstract

Aim:To investigate the possible effect of haemodialysis (HD) on the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of evogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor.Methods: A single-dose, open-label, parallel-group study of eight end-stage renal disease (ESRD) patients and eight matched healthy subjects was conducted. ESRD patients received a single oral dose of evogliptin 5 mg after and before HD with a 2-week washout between each dose, and healthy subjects received a single oral dose of evogliptin 5 mg. Serial blood, dialysate, and urine samples were collected to assess the PK and PD profiles of evogliptin. To compare PK parameters before and after HD, geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were calculated. Results:The GMRs for the maximum concentration and area under the concentration-time curve from time 0 to the last measurable timepoint (AUC last ) of evogliptin when administered before HD compared with after HD were 0.7293 (90% CI 0.6171-0.8620) and 0.9480 (90% CI 0.8162-1.1010), respectively. The maximum DPP-4 inhibitory effect, area under the DPP-4 inhibitory effect-time curve, and time duration of more than 80% DPP-4 inhibition were comparable when evogliptin was administered before and after HD. Compared with healthy subjects, the mean AUC last of evogliptin was approximately 1.4-fold greater in ESRD patients, but the difference is unlikely to affect the safety and efficacy of evogliptin. Conclusion:The effect of HD on the PK and PD characteristics of evogliptin was not clinically significant; therefore, dose adjustment according to HD status is not necessary.

Perfil epidemiológico e tendência temporal da mortalidade por lesões autoprovocadas entre adolescentes e jovens no Brasil, 2013-2022

“…O presente estudo identificou que as taxas de suicídio foram maiores entre adultos jovens e adolescentes. Uma pesquisa internacional realizada com mais de 370 mil estudantes identificou que 37,5% apresentaram ideação suicida (Im;Oh;Suk, 2017). Uma revisão sistemática com meta-análise identificou que fatores como problemas familiares e baixo contato social foram considerados de risco para ideações suicidas.…”

“…Esses resultados são semelhantes com os da literatura, que aponta a prevalência de suicídio entre homens equivale a uma proporção de 2:1 entre os sexos (Cicogna;Hillesheim;Hallal, 2019). A presença de problemas econômicos, desemprego, morar sozinho, não ser casado e falta de religiosidade são associadas a maiores chances de suicídio (Im;Oh;Suk, 2017). Além disso, uso de substâncias como drogas, tabaco e álcool podem explicar as diferenças entre os sexos (Marín-León;Barros, 2003).…”