治疗用碘[^131I]化钠胶囊在格雷夫斯病患者体内的药代动力学及疗效的前瞻性对照研究

A prospective controlled trial for pharmacokinetics and effectiveness of therapeutic sodium iodide （^131I） capsule in patients with Graves disease

目的 比较诊断期及治疗期碘[^131I]化钠胶囊与口服液在格雷夫斯病（GD）患者体内的血液药代动力学及患者甲状腺摄碘率的差异,评价两者治疗GD的疗效及安全性.方法 采用开放、平行、随机、对照的前瞻性临床研究.纳入44例GD患者[男14例,女30例,年龄（33.84±4.96）岁].其中试验组（A组,22例）诊断期口服碘[^131I]化钠口服液,治疗期口服碘[^131I]化钠胶囊;对照组（B组,22例）反之.测定2组诊断期及治疗期服药后0、5、10、20、40和80 min血放射性计数,以及2、4、6和24 h甲状腺摄碘率,采用梯形法计算两者时间曲线的AUC、峰浓度（cmax）及达峰时间（tmax）.观察3、6个月疗效及不良反应.采用SAS 9.3软件对试验数据进行多因素方差分析、t检验及χ^2检验.结果 每组各有1例失访,有效病例每组各21例.诊断期A组血放射性计数占给药放射性计数百分比（OD％）的时间曲线AUC0→t[（450.70±258.00）％·min]小于B组[（684.45±237.00）％·min],cmax[（8.43±4.00）％]低于B组[（13.28±4.20）％],Z=2.640 7、t=3.923 0,均P＜0.01;2组tmax分别为（37.27±23.10）和（34.55±21.30） min,Z=-0.335 9,P＞0.05.治疗期A、B组tmax分别为（46.36±24.98）和（28.64±19.35） min,Z=-2.681 8,P＜0.01;而2组AUC0→t和cmax差异均无统计学意义（t=1.707 4、1.357 4,均P＞0.05）.诊断期及治疗期2组摄碘率AUC0→t、cmax及tmax差异均没有统计学意义（t=0.420 8、1.596 8、0.797 8、1.688 0,Z=0.556 4、-0.013 8,均P＞0.05）.治疗后3个月A组甲状腺功能亢进症（简称甲亢）缓解者占66.7％（14/21）,B组相应比例为61.9％（13/21）,χ^2=0.104,P＞0.05;2组发生甲状腺功能减退症（简称甲减）比例分别为23.8％（5/21）和28.6％（6/21）,χ^2=0.123,P＞0.05.治疗后6个月2组甲亢和甲减发生比例差异也均无统计学意义（χ^2=1.118、1.714,均P＞0.05）.无一例出现不良反应.结论 诊断期和治疗期2种剂型碘[^131I]化钠的血液药代动力学存在一些差异,但并不影响甲状腺24h摄碘率.两者治疗GD的疗效相同,且无不良反应.

Objective To determine the serum pharmacokinetics and radioiodine uptake of sodium iodide （^131I） liquid and capsule in patients with Graves disease（GD）,and to evaluate the effectiveness and safety of these two dosage forms in treating GD.Methods An open,randomized,parallel controlled prospective clinical study was designed.Forty-four patients （14 males,30 females,（33.84±4.96） years） with GD were recruited.The experimental group （group A,n=22） received sodium iodide （131I） liquid in diagnostic period and sodium iodide （131I） capsule in therapeutic period and vice versa （capsule vs liquid） for control group （group B,n=22）.Serum radioactivity （0,5,10,20,40,80 min） and radioiodine uptake （2,4,6,24 h） were measured both in the diagnostic and therapeutic periods.The values of AUC （AUC0→t）,maximum concentration （cmax） and maximum time （tmax） were calculated by trapezium method.Effectiveness and adverse events were evaluated in 3 and 6 months.Analysis of variance,t test and χ^2 test were performed by SAS 9.3.Results There were 21 valid cases in both groups （1 patient was lost in each group）.In diagnostic period,AUC0→t and cmax of percentage of oral dose （OD%） in group A were significantly lower than those in group B：（450.70 ± 258.00） % · min vs （684.45 ± 237.00） % · min,（8.43 ±4.00）% vs （13.28±4.20）%（Z=2.6 407,t=3.9 230,both P〈0.01）.There was no significant difference of tmax between the 2 groups：（37.27±23.10） vs （34.55±21.30） min,Z=-0.335 9,P〉0.05.In therapeutic period,tmax in group A was significantly longer than that in group B：（46.36±24.98） vs （28.64±19.35） min,Z=-2.681 8,P〈0.01.There was no significant difference in neither AUC0→t nor cmax between the 2 groups （t=1.7 074,1.3 574,both P〉0.05）.No significant difference was shown in AUC0→t,cmax and tmax between the 2 groups in both diagnostic period and therapeutic period（t=0.420 8,1.596 8,0.797 8,1.688 0,Z=0.556 4,-0.013 8,all P〉0.05）.Three months after treatment,14 out of 21 cases （66.7%） remitted in group A while 13 patients （61.9%） remitted in group B（χ^2=0.104,P〉0.05）.Five patients（23.8%） developed hypothyroidism in group A while 6 patients （28.6%） in group B （χ^2=0.123,P〉0.05）.Six months after treatment,the percent of hypothyroidism and remission were not significantly different between group A and B （χ^2=1.118,1.714,both P〉0.05）.No adverse event occurred in both groups.Conclusions Though pharmacokinetics between the two dosage forms showed significantly difference,outcomes were similar.Besides,no severe adverse event was observed in both groups.