Efficacies of sirolimus (rapamycin) and cyclosporine in allograft vascular disease in non-human primates: trough levels of sirolimus correlate with inhibition of progression of arterial intimal thickening.

摘要: We investigated the efficacies of sirolimus (rapamycin) and cyclosporine for inhibition graft vascular disease (GVD) in cynomolgus monkey recipients aortic allografts. Increases arterial intimal thickening midgraft (six consecutive cross-sections) after transplantation were quantified by serial intravascular ultrasound (IVUS) from day 21 to 105. These data enabled correlations between changes indexes [II = (intimal area/vessel area) × 100] trough levels be determined. Eighteen received no immunosuppression 6 weeks allow alloimmune injury occur. On 45, monkeys treated daily with (n 6) or 6); six remained untreated. II increased significantly 63 105 untreated cyclosporine, whereas did not have a significant increase (P 0.008, P 0.006, NS; paired t-test). The change days was greater compared sirolimus-treated 0.13; one-way ANOVA, 0.012 Tukey's post hoc test); other pairwise comparisons significant. Mean ± SEM 43 7 ng/ml 562 20 ng/ml, respectively. Sirolimus levels, but correlated inversely 42 (r2 0.73, 0.03). This non-human primate study shows that depends on provides rationale clinical trials control GVD organ transplant recipients.