Sirolimus observational studies

Observational studies In a single-center study in 86 liver transplant recipients taking sirolimus, eight had too short a follow-up to include them in the analysis of long-term results, 38 were treated with sirolimus as the main immunosuppressant, and the other 40 took sirolimus-I-caldneurin inhibitors [124. Of the 86 patients, 82 developed a total of 92 adverse reactions hyperlipidemia ( =44), leg edema ( =20), anemia ( = 12), oral ulcers (n=5), rashes (n=5), diarrhea and leukopenia (two each), and thrombocytopenia and cardiomyopathy (one each). Sirolimus was withdrawn because of severe adverse reactions in seven cases, including generalized rashes (n=3), and cardiomyopathy, leg edema, diarrhea, anemia, and oral ulcers (one each). Rashes and cardiomyopathy developed soon after sirolimus introduction, the other adverse reactions usually had a gradual onset of several months. The leg edema in 20 patients resolved spontaneously in 7,... 

Sirolimus has also been used in the production of sirolimus-eluting stents. These stents are used to treat obstructive coronary arteries. The rationale for the use of sirolimus in these stents is due to its antiproliferative activity. It has also received attention for cancer treatment due to its antiproliferative effects. In animal studies, sirolimus has shown some potential in the treatment of cancer where in combination with doxorubicin, a remission for Akt-positive lymphomas has been observed. 

The first clinical study was the RAVEL trial, which showed that no cases of restenosis were observed with the DES, but 26.6% of BMS cases suffered from restenosis [31]. A 3 year follow-up of the RAVEL study showed sustained clinical benefits [35], during which another set of trials called the SIRIUS study compared the safety and efficacy of the sirolimus eluting stent with two smaller studies that were performed in Europe (E-SIRIUS) and Canada (C-SIRIUS) [36-39]. The combined results showed a reduction in in-stent restenosis from 38.5% (BMS) to 3.1% (sirolimus eluting stent). 

In an in vitro drug release study, an initial burst release of more than 40% of sirolimus from the control stents was observed on the first day of the experiment, whereas no apparent burst release from the experimental stents occurred (Fig. 14) [166]. After 10 days, the cumulative percentages of drug that were released from the... 

Recent studies have reported that sirolimus reduces neointimal formation by inhibiting the proliferation and migration of VSMC and delays the normal healing processes of the injured arterial wall [147]. In the control group, poor endothehal cell junction formation (Fig. 16b) [166] and thrombus-hke substance deposition around the stent stmts (indicated by the arrow in Fig. 16b, inset) were observed at 6 weeks after implantation, possibly owing to the adverse side effects of the initial... 

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