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“Introduction Idiopathic membranous nephropathy (IMN) is the most representative disease associated with steroid-resistant nephrotic syndrome (SRNS)

in adults. Although the combination of steroids and immunosuppressants, e.g., cyclophosphamide (CPA) and chlorambucil, has been reported to induce and maintain remission in randomized controlled studies [1, 2], the beneficial effects remain controversial because of the harmful side-effects of the alkylating agents. Moreover, in our cohort study of 1,000 cases in Japan, combined treatment with steroids and CPA was not superior to steroid monotherapy [3]. Recently, cyclosporine (CyA), a calcineurin inhibitor, has been introduced as an effective agent for SRNS, and several randomized

controlled trials (RCTs) LY333531 mw on the combination of steroids and CyA showed significant remission rates [4–6]. However, it has been recognized that clinical response does not correlate well with the administration dose. Accordingly, careful attention to the CyA concentration in blood is essential for the optimization of

therapy [7]. For this reason, the mafosfamide blood concentration of the drug was previously monitored at the trough level before administration (C0) because the absorption of CyA is highly affected by bile acid and other factors of absorption when the original CyA formulation was used orally [8]. The introduction of CyA microemulsion preconcentrate (MEPC) minimized the influence of bile acid and stabilized the absorption profile (AP) of CyA [9]. In a transplantation study, the area under the blood concentration–time curve up to 4 h after administration of CyA (AUC0–4) was believed to accurately express CyA absorption and sensitively predict the effect of CyA [10]. Moreover, the CyA blood concentration at 2 h post dose (C2) was recommended as the best surrogate single-sample marker for routine monitoring [10]. Recent studies have shown that once-a-day administration is more advantageous than the conventional twice-a-day administration, because the former provides an AP showing the peak blood concentration of CyA, which may facilitate the remission of SRNS and prevent chronic CyA nephrotoxicity [11, 12]. In addition, preprandial administration of CyA may be favorable for Ro 61-8048 supplier achieving a stable blood concentration because CyA is absorbed without the influence of food ingestion [12, 13].

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