FK 506 versus cyclosporin in the prevention of renal allograft rejection – European pilot study: six-week results

Abstract

FK 506 was compared with cyclosporin in a randomised trial in good-risk cadaveric renal transplant recipients. The objective was to evaluate whether oral FK 506 dosing was viable and whether blood concentrations in the range 10-20 ng/ml would prove to be practical. Thirty-one adult patients were randomised to FK 506 and 16 to cyclosporin. Both groups received an identical regimen of azathioprine and corticosteroids. Serum creatinine concentrations decreased rapidly in both groups with mean values below 200 mumol/l within 2 weeks. One graft in the cyclosporin group was lost due to renal vein thrombosis. During the 6-week study period, 19.4% of patients on FK 506 and 31.3% on cyclosporin experienced acute rejection. One patient in each group experienced corticosteroid-resistant rejection that responded to anti-lymphocyte therapy. Infections were reported in 51.6% of the FK 506 group compared with 37.5% of the cyclosporin group. The spectrum of adverse events was similar in both groups. However, minor neurological disorders were more common in the FK 506 group (54.8% versus 6.3%) whereas hypertension was less common (48.8% versus 75.0%). The results indicate that oral FK 506 rapidly achieves therapeutic blood concentrations and is an effective immunosuppressant for the initial treatment of renal allograft recipients.

Single-center experience with tacrolimus versus cyclosporine-Neoral in renal transplant recipients

“…Although mean arterial pressure was comparable, the need for anti-hypertensive drugs was lower in the tacrolimus group and more patients were without anti-hypertensive treatment. This is in accordance with previous reports in which tacrolimus was compared to both Sandimmune [17,33,40,42] and Neoral [19].…”

“…In our study, renal function in patients with a functioning graft 12 months after transplantation was comparable with tacrolimus and Neoral. This is in accordance with previous reports in which tacrolimus was compared to Sandimmune [17,26,33,40,42,52] or Neoral [lo, 291. In contrast, Jurewicz reported a lower serum creatinine in the tacrolimus group than in the Neoral group [19].…”

“…Acute-rejection-free survival was halved in the tacrolimus group. The rate of acute rejection in the tacrolimus group was 18.5 YO, comparable to the 19.4 % [40] and 25.9% [26] in former European multicenter trials. By participating in those trials, our center acquired a lot of experience with tacrolimus.…”

“…In former trials, tacrolimus-based immunosuppression had been shown to be superior to cyclosporine (Sandimmune) with regard to the prevention of acute and steroid-resistant rejection [17, 26,33,40,521. Neoral, the new formulation of cyclosporine, has proven to be superior to Sandimmune in the prevention of acute rejection [20,31,34].…”

Chrono and clinical pharmacokinetic study of tacrolimus in continuous intravenous administration

“…In prospective and historically controlled studies of primary therapy, tacrolimus has generally demonstrated greater efficacy than the conventional formulation of cyclosporine A (CyA) in preventing episodes of acute rejection and allowed a reduction in corticosteroid use. 5,6 Acute rejection rates were also significantly reduced with tacrolimus in a large-scale randomized study of kidney transplantation. 7 Although short-term graft survival is similar on tacrolimus and CyA, tacrolimus is also an effective rescue therapy for renal allograft rejection during CyA therapy.…”