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HPLC–MS/MS-based analysis of everolimus in rabbit aqueous humor: pharmacokinetics of in situ gel eye drops of suspension

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Aim: Everolimus is an inhibitor of mTOR which is derived from rapamycin. Its high corneal permeability and bioavailability makes it an effective treatment for ocular disorders. To study the pharmacokinetics of in situ gel eye drops of everolimus suspension after ocular administration in rabbit aqueous humor, we developed a rapid and reliable HPLC–MS/MS method.

Keywords: aqueous humor, everolimus, HPLC–MS/MS, pharmacokinetics


Everolimus is a 40-O-[2-hydroxyethyl] derivative of sirolimus and an inhibitor of mTOR kinase (Figure 1). It is an active immunosuppressor and antiproliferative macrolide [1]. It has rapid absorption kinetics and its bioavailability is higher than sirolimus (everolimus 16–20% vs sirolimus 10–14%) [2,3]. Based on its pharmacokinetic characteristics, the elimination half-life of everolimus is shorter (32 h) than that of sirolimus (62 h). Hence, no loading dose is needed for everolimus and the steady state is achieved faster [4–7]. It inhibits the proliferation and cloning of antigen-activated T cells by a mechanism involving FK506 binding with protein-12 to suppress mTOR complex-1 activity [8]. In the recent years, everolimus is used as an immunosuppressant and anticarcinogen for organ transplantation such as cardiac, renal cell carcinoma, neuroendocrine tumors and renal angiomyolipoma [9,10]. In addition, an everolimus stent is clinically used to inhibit monocyte/macrophage migration [11,12].

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