Cyclosporine: vital in today's transplantation, but questions remain about tomorrow

Article Abstract:

At a recent meeting of the International Congress of the Transplantation Society, the future use of cyclosporine was debated. This drug suppresses the immune system, thereby reducing graft rejection; its introduction less than 10 years ago made transplantation on a wide scale possible. However, cyclosporine is toxic to the kidney, and this effect that may not become evident for several years. Prior to the introduction of cyclosporine, transplant patients were treated with the combined regimen of azathioprine and prednisone (a steroid), which is now considered ''second best''. Results from studies describing the toxicity of cyclosporine are presented; these statistics are probably reported with increasing frequency, since the drug has only been in use for 10 years, and kidney disease may not develop for decades. Unfortunately, lower doses of cyclosporine, in use since 1984, do not appear to prevent the problem. Some physicians believe that substitutes for cyclosporine should be found, and the drug should be withdrawn. On the other hand, study results report similar kidney function in patients maintained for eight years or more on cyclosporine or the azathioprine/prednisone combination. In addition, if patients can avoid long-term use of steroid drugs (which may be possible, according to new evidence presented at the meeting), many of the serious complications of transplantation would not occur. A recent study of 521 transplant patients uncovered no ill effects on graft or patient survival in those who received cyclosporine plus placebo (an inactive drug), compared with patients who were given cyclosporine plus prednisone. In fact, the former group had a lower incidence of high blood pressure, diabetes, and orthopedic complications. Calvin Stiller, chief of the Multiorgan Transplant Service at a hospital in Canada, went so far as to say that steroids continue to be prescribed with cyclosporine because of physicians' ''emotional attachment'' to the method of treatment. New drugs are under development. Researchers recognize, however, that immunosuppression, which tampers with fundamental cellular mechanisms, is likely to always be associated with serious side effects. (Consumer Summary produced by Reliance Medical Information, Inc.)

Conferences, meetings and seminars, Steroids (Drugs)

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New antirejection drugs anticipated

Article Abstract:

Patients receiving heart-lung, heart, or lung transplants frequently ''reject'' the transplanted tissue because their immune system perceives it as a foreign substance. Immunosuppressant drugs are usually given to transplant patients to prevent tissue rejection by inhibiting this reaction at the cellular level. Cyclosporine is a common, effective immunosuppressant that has been important in converting transplantation from a laboratory curiosity to a standard medical practice. Recently, more effective and safer agents that are molecularly similar to cyclosporin have been developed. Included in this group of promising immunosuppressants are FK506, RS-61443 and rapamycin. It is particularly exciting to researchers that these drugs affect different stages of the rejection phenomenon. Thus, they may be used together to enhance immunosuppression and to lower the risk of serious side effects. However, one combination, cyclosporin and FK506, is highly toxic and must be avoided. These drugs are still classified as experimental; carefully controlled random trials must be carried out before they can be approved for general use. If the drugs pass these tests successfully, a great enhancement in the outcome of organ transplantation is expected. FK506 has been tested more than the other new agents, and is regarded by some as the most potent immunosuppressant in clinical use. One preliminary study of 89 liver transplant patients, who received FK506 and steroids, reported graft survival of 86 percent and patient survival of 92 percent after a follow-up period of 42 to 171 days. Fifteen members of this group were receiving their second to sixth liver transplant. This result is considerably better than the typical outcome of liver transplantation with cyclosporin treatment. The article also discusses the source and some preliminary clinical findings of the other two newly developed immunosuppressants: RS-61443 and Rapamycin. Despite the promise of these new drugs, cyclosporin remains the ''gold standard'' for immunosuppression, and will most probably continue to be the clinical drug of choice for a number of years. (Consumer Summary produced by Reliance Medical Information, Inc.)

Physiological aspects, Rapamycin, FK 506

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Cyclosporine-ketoconazole combination offers promise in reducing antirejection therapy costs

Article Abstract:

Kidney transplant patients routinely receive immunosuppressive agents to prevent organ rejection. The combined use of two immunosuppressants, cyclosporine and ketoconazole, has been discouraged by pharmaceutical manufacturers because of resulting high cyclosporine levels in the blood; however, researchers have found a potential benefit to the drug interaction. In one study, physicians were able to reduce the cyclosporine dose by 70 percent in the first week of therapy and up to 88 percent after 18 months. To prevent rejection of the transplant, patients must continue cyclosporine therapy for the rest of their lives. This therapy is an expensive component of the management of patients with organ transplants and the new combination therapy may ease the financial burden. Researchers found the combination to be effective, safe, and less expensive than cyclosporine alone, and this combination is being used in patients receiving other organ transplantations. (Consumer Summary produced by Reliance Medical Information, Inc.)

Drug therapy, Drug synergism

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