Le Mauff B, Le Meur Y, Hourmant M, Debray M, Boeffard F, Alberici G, Soulillou J P, Scherrmann J M
INSERM U437, Service de Néphrologie et Immunologie Clinique, Nantes, France.
Kidney Int Suppl. 1996 Jan;53:S44-50.
25.3, a mouse IgG1 monoclonal antibody (MoAb), directed at the alpha chain of the LFA1 molecule (CD11a) has been used in prophylaxis of rejection in recipients of cadaveric kidney graft. Promising clinical results have been obtained for both tolerance and efficacy [1]. The aim of this trial was to determine the optimal dosage, base on a pharmacokinetic-pharmacodynamic analysis of the data obtained from the 15 patients included in this dose-searching study. Biological parameters, such as circulating levels and functional inhibition (as detected in an adhesion assay of patient lymphocytes), were measured during and after treatment. A Hill relation was calculated between the effect and the concentration measured and led us to select a 15 mg/day dose for further clinical trials, with a loading dose of 30 mg. An additional group receiving this protocol was submitted to the same calculation, and the results from this last group were in agreement with this previous analysis.
一种针对淋巴细胞功能相关抗原1分子（CD11a）α链的小鼠IgG1单克隆抗体（MoAb）25.3，已被用于预防尸体肾移植受者的排斥反应。在耐受性和疗效方面均已取得了有前景的临床结果[1]。本试验的目的是基于对纳入该剂量探索研究的15例患者所获数据的药代动力学-药效学分析，确定最佳剂量。在治疗期间及治疗后，测量了生物学参数，如循环水平和功能抑制（在患者淋巴细胞的黏附试验中检测）。计算了效应与所测浓度之间的希尔关系，这使我们选择15毫克/天的剂量用于进一步的临床试验，负荷剂量为30毫克。接受该方案的另一组也进行了同样的计算，最后一组的结果与之前的分析一致。
