Using Caco-2 cell monolayers expressing CYP3A4, we investigated the interplay between metabolism and transport on the first-pass intestinal extraction of the immunosuppressant sirolimus, a CYP3A4/P-glycoprotein (P-gp) substrate. Modified Caco-2 cells metabolized [(14)C]sirolimus to the predicted amounts of CYP3A4-mediated products based on CYP3A4 content, which was approximately 20% of that mea...

INTRODUCTION AND OBJECTIVES The angiographic and clinical efficacy of polymer-free sirolimus-eluting stents vs polymer-based paclitaxel-eluting stents remain a matter of debate. We sought to investigate angiographic and clinical measures of efficacy of polymer-free sirolimus-eluting stents vs polymer-based paclitaxel-eluting stents. METHODS Patient data from the randomized intracoronary stent...

CYP3A4-transfected Caco-2 cells were used as an in vitro system to predict the importance of drug metabolism and transport on overall drug absorption. We examined the transport and metabolism of two drugs; midazolam, an anesthetic agent and CYP3A4 substrate, and sirolimus, an immunosuppressant and a dual CYP3A4/P-glycoprotein (P-gp) substrate, in the presence of cyclosporine (CsA, a CYP3A4/P-gp...

BACKGROUND Inhibitors of mTOR, such as sirolimus, have been shown to induce thymus involution and inflammatory lung disease in mice. The latter effect supports the role of this serine/threonine kinase in ameliorating lung inflammation. Other studies have shown sirolimus reduces/delays lung disease associated with various strains of influenza A virus (IAV). Thus, the effects of mTOR inhibitors o...

BACKGROUND The long-term effects of treatment with sirolimus-eluting stents, as compared with bare-metal stents, have not been established. METHODS We performed an analysis of individual data on 4958 patients enrolled in 14 randomized trials comparing sirolimus-eluting stents with bare-metal stents (mean follow-up interval, 12.1 to 58.9 months). The primary end point was death from any cause....

Varghese, Zac, Ray Fernando, John F. Moorhead, Stephen H. Powis, and Xiong Z. Ruan. Effects of sirolimus on mesangial cell cholesterol homeostasis: a novel mechanism for its action against lipid-mediated injury in renal allografts. Am J Physiol Renal Physiol 289: F43–F48, 2005. First published March 15, 2005; doi:10.1152/ajprenal.00181.2004.—Lipoprotein abnormalities are present in a high propo...

BACKGROUND We hypothesize that the combination of an mTOR inhibitor, sirolimus, with a well-known cytotoxic agent, cyclophosphamide, provides a well-tolerated and promising alternative treatment for advanced, differentiated thyroid cancers (DTC). METHODS This retrospective review extracted data from patients treated for advanced DTC at the University of Michigan Comprehensive Cancer Center fr...

I N RENAL transplant recipients, sirolimus has been studied extensively in combination with cyclosporine,l but relatively few published studies have looked at the combination of sirolimus and tacrolimus?-S We performed a pilot trial of tacrolimus, sirolimus, and steroids, without antibody induction and with protocol biopsies, to look at the safety and efficacy of this combination. This report d...

Background: The introduction of sirolimus has provided the opportunity to develop an immunosuppressive regimen without the nephrotoxic calcineurin inhibitors. Methods: we conducted a first trial in 30 renal allograft recipients. Ten patients were followed prospectively and received sirolimus, to achieve a target blood level of 10 to 15 ng/ml, induction therapy with one dose of daclizumab, low-d...