In clinical studies, single doses of up to 12 times (and multiple doses of up to 5 times) the recommended dosage of difelikefalin were administered in subjects undergoing hemodialysis.L36395 These patients experienced a dose-dependent increase in adverse reactions, including gastrointestinal effects and CNS depressant effects. In the event of overdosage, difelikefalin is dialyzable - 4 hours of high-flux hemodialysis effectively clears approximately 70-80% of the drug from plasma, and levels are likely to be undetectable following a second cycle.L36395
Difelikefalin (CR845) is an agonist of kappa opioid receptors (KORs) useful in the treatment of pruritus secondary to chronic kidney disease. KORs were first associated with itching in 1984.A237610 Further investigations revealed that dynorphins, endogenous agonists of KORs, work to inhibit the itching sensation at the spinal cord level, and scratching could be elicited in mouse models with the administration of KOR antagonists.A237610 These revelations led to the study of KOR agonists as a potential treatment option in patients suffering from pruritic conditions.
Pruritus associated with chronic kidney disease (also called uremic pruritus) affects 50-60% of all patients on dialysis and 25% of non-dialysis patients with chronic kidney disease.A237615,A237620 The clinical burden of uremic pruritus in this patient population is being increasingly recognized as contributing to a significant reduction in patient quality of life, poor outcomes, and even mortality.A237620 Options for therapy are limited - with no FDA-approved treatments, off-label gabapentin was the most evidence-based and widely available treatment.A237620
Difelikefalin received FDA approval in August 2021 (under the brand name Korsuva), becoming the first FDA-approved therapy for patients with chronic kidney disease suffering from uremic pruritus.L36420,L36395 Difelikefalin was later approved by the EMA in April 2022 for the same indication.L41665
Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).
drugbank-id dan name pada skema XML DrugBank.targets/target yang memuat polipeptida sasaran.gene-name dan varian snp-effects.Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.