PURPOSE Sirolimus is the eponymous inhibitor of the mTOR; however, only its analogs have been approved as cancer therapies. Nevertheless, sirolimus is readily available, has been well studied in organ transplant patients, and shows efficacy in several preclinical cancer models. EXPERIMENTAL DESIGN Three simultaneously conducted phase I studies in advanced cancer patients used an adaptive esca...

BACKGROUND Sirolimus is a potent blocker of mammalian target of Rapamycin (MTOR), with anti proliferative activity. Its potential for the management of oral cancer has been suggested. Our aim was to establish an analytical method for determining sirolimus levels in human saliva and to calculate the blood vs. saliva ratio in individuals using sirolimus chronically in order to evaluate the total ...

Immunosuppressants require therapeutic drug monitoring because of their narrow therapeutic index and significant inter-individual variability in blood concentrations. This variability can be because of factors like drug-nutrient interactions, drug-disease interactions, renal-insufficiency, inflammation and infection, gender, age, polymorphism and liver mass. Drug monitoring is widely practiced ...

The present study aimed to investigate the effect of Eudragit® E/HCl (E-SD) on the degradation of sirolimus in simulated gastric fluid (pH 1.2) and to develop a new oral formulation of sirolimus using E-SD solid dispersions to enhance oral bioavailability. Sirolimus-loaded solid dispersions were fabricated by a spray drying process. A kinetic solubility test demonstrated that the sirolimus/E-SD...

BACKGROUND The aim of this study was to improve the physicochemical properties and bioavailability of poorly water-soluble sirolimus via preparation of a solid dispersion of nanoparticles using a supercritical antisolvent (SAS) process. METHODS First, excipients for enhancing the stability and solubility of sirolimus were screened. Second, using the SAS process, solid dispersions of sirolimus...

The vast majority of glomerular filtrated phosphate is reabsorbed in the proximal tubule. Posttransplant phosphaturia is common and aggravated by sirolimus immunosuppression. The cause of sirolimus induced phosphaturia however remains elusive. Male Wistar rats received sirolimus or vehicle for 2 or 7 days (1.5mg/kg). The urine phosphate/creatinine ratio was higher and serum phosphate was lower ...

Small intestinal metabolism and transport of sirolimus, a macrolide immunosuppressant with a low and highly variable oral bioavailability, were investigated using small intestinal microsomes and intestinal mucosa in the Ussing chamber. After incubation of sirolimus with human and pig small intestinal microsomes, five metabolites were detected using high performance liquid chromatography/electro...

PURPOSE The aim of the present study was investigating the effects of three anti-inflammatory drugs, on Sirolimus protein biding. The binding site of Sirolimus on human serum albumin (HSA) was also determined. METHODS Six different concentrations of Sirolimus were separately exposed to HSA at pH 7.4 and 37°C. Ultrafiltration method was used for separating free drug; then free drug concentrati...

The toxic effect of the macrolide immunosuppressant sirolimus on cell metabolism of primary astrocytes was studied by multinuclear NMR spectroscopy of viable cells and perchloric acid (PCA) extracts and compared to the effects of the immunosuppressant cyclosporine. The addition of 5 mg/L sirolimus (5.5 mumol/L) induced swelling of primary astrocytes to 110% of the original volume. Alteration in...

Sirolimus is increasingly being used in neonates and infants, but the mechanistic basis of age-dependent changes in sirolimus disposition has not been fully addressed yet. In order to characterize the age-dependent changes, serial sirolimus clearance (CL) estimates in individual young pediatric patients were collected and analyzed by population modeling analysis. In addition, sirolimus metaboli...