| Abstract: | The chemistry, pharmacokinetics, mechanism of action, clinical efficacy in organ transplants, adverse effects, and dosage and administration of cyclosporine, a new immunosuppressant, are reviewed. Advice on counseling patients who take the drug is also included. Cyclosporine is a cyclic undecapeptide with a high molecular weight. Its absorption from the gastrointestinal tract is slow, variable, and incomplete. Cyclosporine is highly protein bound and almost completely eliminated by hepatic metabolism. Its half-life is variable, and it has a volume of distribution of approximately 4 liter/kg and a poorly defined therapeutic range. Cyclosporine acts by blocking T-lymphocyte function without causing myelosuppression. Several randomized prospective trials have compared cyclosporine with standard immunosuppressive drug regimens in kidney and liver transplantations. A European Multicenter Trial treated 117 patients with cyclosporine alone and 115 patients with azathioprine and steroids. Graft survival rates at 11 months were 73% in the cyclosporine group and 53% in the control group. A Canadian Multicenter Trial Group, which studied 209 patients in two groups, found cyclosporine and prednisone to be superior to azathioprine and prednisone therapy. Graft survivals were 83.5% and 67% at nine months. Several studies of hepatic allograft recipients and of cardiac transplantations have found that cyclosporine and low-dose steroid therapy can lead to improved results. The adverse effects of cyclosporine include nephrotoxicity, hepatotoxicity, and electrolyte elevations. The dosage must be individualized. Most patients tolerate initial i.v. doses of 5 mg/kg and oral doses of 14-18 mg/kg. The exact indications for cyclosporine immunosuppression are still being defined for organ transplant recipients. Cyclosporine will likely play an important role in the improvement of transplantation results in the future. |
