Interspecies scaling of clearance and volume of distribution for horse antivenom F(ab′)2
Interspecies scaling of clearance and volume of distribution for horse antivenom F(ab′)2
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DOI：
10.1006/taap.1997.8363
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发表时间：
1998-06-01
影响因子：
3.8
通讯作者：
Scherrmann, JM
中科院分区：
文献类型：
--
作者：
Bazin-Redureau, M;Pepin, S;Scherrmann, JM
F（ab’）(2)片段有时在治疗或诊断方面优于整个IgG。临床前药物开发研究在用于人类之前是必要的。在这里，我们提出了一种异速测量方法，在三种哺乳动物中预测F(ab')(2)在人类体内的药代动力学参数。研究了碘125标记的马抗蛇毒血清F（ab’）(2)片段在小鼠、大鼠和家兔中10mg /kg剂量的血浆处理。利用异速生长法，我们发现与体重相关的药代动力学参数为分布体积(Vd(c) (ml) = 0.125 W-0.87；Vd(ss) (ml) = 0.251 W-0.87；Vd(beta) (ml)= 0.290 W-0.87, r(2) = 1)，总清除率(CI,, (ml/h) = 0.049 W-0.53, r(2) = 0.99)，末端半衰期（t1/2 beta (h) = 4.35 W-0.33）。F(ab')(2)等离子体浓度-时间数据绘制为复杂的Dedrick关系是重叠的。使用这些异速测量技术，对体重为70kg的受试者，Vd（ss）、Vd（β）、Cl-tot和t1/2 β分别计算为4.12升、4.78升、19.07 ml/h和7.2天。预测的人体药代动力学参数的分布体积值与Hnatowich等人报告的值相当（Cancer res47, 6111-6117, 1987）： 3.5升。然而，间隙比Hnatowich等人（130 mVh）和Ho等人(C) 1998年学术出版社给出的值低6倍。
F(ab')(2) fragments are sometimes preferred to whole IgG for therapeutic or diagnostic uses. Preclinical pharmaceutical development studies are necessary before their use in humans. Here we propose an allometric approach among three mammalian species to predict F(ab')(2) pharmacokinetic parameters in humans. Plasma disposition of horse antivenom F(ab')(2) fragments labeled with iodine 125 was studied at a dose of 10 mg/kg iv in mice, rats, and rabbits. Using the allometric method, we demonstrate that the pharmacokinetic parameters that correlated with body weight were distribution volume (Vd(c) (ml) = 0.125 W-0.87; Vd(ss) (ml) = 0.251 W-0.87; Vd(beta) (ml)= 0.290 W-0.87, r(2) = 1), total clearance (CI,, (ml/h) = 0.049 W-0.53, r(2) = 0.99), and terminal half-life (t1/2 beta (h) = 4.35 W-0.33). The F(ab')(2) plasma concentration-time data plotted as a complex Dedrick relationship were superimposable. Using these allometric techniques, Vd(ss), Vd(beta), Cl-tot and t1/2 beta were calculated as 4.12 liter, 4.78 liter, 19.07 ml/h, and 7.2 days, respectively, for a human subject of 70 kg body wt. Predicted human pharmacokinetic parameters were comparable for volume of distribution with the value reported by Hnatowich et al. (Cancer Res. 47, 6111-6117, 1987): 3.5 liter. However, the clearance was six-fold lower than values given by Hnatowich et al. (130 mVh) and Ho ef al. (C) 1998 Academic Press.