Todo S, Demetris A, Ueda Y, Imventarza O, Cadoff E, Zeevi A, Starzl T E
Department of Surgery, University of Pittsburgh, Pa.
Surgery. 1989 Aug;106(2):444-50; discussion 450-1.
FK 506 was tested in unrelated baboons submitted to renal transplantation and bilateral native nephrectomy. Untreated baboons died after 9.2 +/- 4.0 SD days. When FK 506 was given orally for 90 days, survival with the optimum dose was 74.6 +/- 28.9 days; this allowed maximum credit for each individual animal of 90 days. A 3-day course of intramuscular FK 506 started on postoperative day 4 allowed 1- to 2-month survival. Delayed rejection in these baboons as well as in those treated daily for 90 days with FK could sometimes be reversed temporarily with a second 3-day course. The doses required for a good therapeutic effect were 10 times greater in baboons than in dogs, a finding that may reflect a species difference of lymphocyte sensitivity to this drug. FK appeared to be relatively nontoxic in subhuman primates, and it remains a promising drug for clinical trial.
对接受肾移植和双侧自体肾切除的无关狒狒进行了FK 506测试。未经治疗的狒狒在9.2±4.0标准差天数后死亡。当口服FK 506 90天时,最佳剂量下的存活时间为74.6±28.9天;这使得每只动物最多可计90天。术后第4天开始为期3天的肌肉注射FK 506疗程可使存活1至2个月。这些狒狒以及用FK每日治疗90天的狒狒中的延迟排斥反应,有时可通过第二个3天疗程暂时逆转。狒狒达到良好治疗效果所需的剂量比狗大10倍,这一发现可能反映了淋巴细胞对该药物的种属敏感性差异。FK在非人灵长类动物中似乎相对无毒,它仍是一种有前景的用于临床试验的药物。