The contributions of cytochrome P450 3A (CYP3A) and P-glycoprotein to sirolimus oral bioavailability in rats were evaluated by coadministration of sirolimus (Rapamune) with the CYP3A inhibitor ketoconazole or the P-glycoprotein inhibitor D-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS). Groups of six male Sprague-Dawley rats (250-300 g) were administered Rapamune (1 mg/kg) by oral...

BACKGROUND Transplant recipients in whom cutaneous squamous-cell carcinomas develop are at high risk for multiple subsequent skin cancers. Whether sirolimus is useful in the prevention of secondary skin cancer has not been assessed. METHODS In this multicenter trial, we randomly assigned transplant recipients who were taking calcineurin inhibitors and had at least one cutaneous squamous-cell ...

Recently, sirolimus, an inhibitor of mammalian target of rapamycin, was reported to decrease chylous effusion in patients with lymphangioleimyomatosis (LAM). We herein report a case of a 34-year-old woman with LAM who developed refractory chylothorax and chylous ascites during sirolimus therapy. In this case, to reduce chylous effusion, we administered octreotide, which is often used to control...

BACKGROUND Sirolimus is recently reported to have antitumour effects on a large variety of cancers. The present study was performed to investigate sirolimus's ability to inhibit growth in T24 bladder cancer cells. METHODS T24 bladder cancer cells were treated with various concentrations of sirolimus. MTT assay was used to evaluate the proliferation inhibitory effect on T24 cell line. The viab...

OBJECTIVES Report a case of sirolimus induced granulomatous pneumonitis. BACKGROUND Sirolimus is used in clinical transplantation as an immunosuppressive agent. Pulmonary toxicity does occur, but only a few cases of sirolimus associated granulomatous interstitial pneumonitis have been reported. METHODS Case report and literature review. RESULTS This 53-year-old woman with ESRD from polycy...

OBJECTIVES This study evaluated the analytical characteristics of the new Abbott microparticle enzyme immunoassay (MEIA) for sirolimus. DESIGN AND METHODS The protocol consisted of nine sections: evaluation of antibody specificity, linearity, detection limit, quantification limit, endogenous interferents, exogenous interferents, precision, proficiency testing panel, and method comparison. R...

PURPOSE The purpose of this study is to elicit the role of oral low-dose sirolimus as a corticosteriod-sparing agent for active uveitis. METHODS A retrospective, interventional case series was performed by reviewing the clinical records of all patients treated with oral, low-dose sirolimus (1-4 mg daily) for severe uveitis. Data reviewed included symptomatic improvement, Snellen best-correcte...

We report a successful pregnancy in a patient with longstanding LAM on treatment with sirolimus. During temporary discontinuation fo sirolimus in early pregnancy, lung function declined but recovered after resumption of sirolimus. Pregnancy was complicated by a persistent pneumothorax which was treated surgically postnatally. The child has had a normal development despite exposure to low dose s...

Sirolimus is an approved anti-rejection agent following liver or kidney transplantation that works through inhibition of the mammalian target of rapamycin (mTOR). As sirolimus functions through a pathway independent of calcineurin inhibition, it may have less potential for nephrotoxicity and carcinogenesis. That being said, there are a myriad of potential adverse effects reported with sirolimus...

BACKGROUND Sirolimus is an immunosuppressive drug recently developed for organ transplantation. Its mechanism of action, independent of calcineurin, is different from that of cyclosporine and tacrolimus, two calcineurin inhibitors (CIs). Because the toxicity of CIs is partly the result of calcineurin blockade, sirolimus exhibits a different toxicity profile. In this study, we evaluated the prof...