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Published on 2 June 2008

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Sirolimus’ long-term promise

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New research from the University of California, San Diego, Department of Medicine, Division of Nephrology, shows that the anti-rejection drug sirolimus (brand name Rapamune) may help prolong the clinical benefit of transplanted kidneys and delay rejection, especially in patients who do not regularly take their prescribed medications.

While the transplant field has been highly successful at reducing rejection and graft loss in the first year, post-transplant, reducing risk for graft rejection in the long-term has proved more difficult.

The findings were presented at the 2008 American Transplant Congress (ATC), in Toronto on 31 May 2008, by Cheri Ye MD, who was mentored by Robert Steiner MD, professor of medicine, and Director of Transplant Nephrology.

“No one is perfect at taking medications,” explained Steiner. “But missing doses of immunosuppression, or not taking full doses each day, will bring about gradual rejection of kidney transplants that is almost impossible to detect in its early stages. Long-acting drugs like sirolimus may help with this problem.”

A team of five UC San Diego investigators reported a careful assessment of immune function at “trough” levels (lowest daily levels) of the three most commonly used immunosuppressive drugs, using an assay (ImmuKnow/Cylex) designed specifically to measure the degree of immunosuppression at any given time. Lower “mitogenic response” meant better immunosuppression and more protection from rejection. On average, the participants – 160 kidney transplant patients – were 6.4 years out from their transplant.

At these trough levels of drug in the blood stream, the assay demonstrated that sirolimus caused a significantly lower level of mitogenic response, and results appeared to be stable in individual patients over time.

“This study was not commercially funded,” added Steiner. “We just wanted to confirm what we suspected from experience in our transplant clinic, where we focus on compliance in many ways to help our patients keep their kidneys functioning well. We showed that when the daily dose is wearing off and another dose is due to be taken, patients taking sirolimus could be more protected against rejection than other commonly used agents.”

University of California, San Diego, Department of Medicine



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