Brocks D R, Freed M I, Martin D E, Sellers T S, Mehdi N, Citerone D R, Boppana V, Levitt B, Davies B E, Nemunaitis J, Jorkasky D K
SmithKline Beecham Pharmaceuticals, Department of Drug Metabolism, King of Prussia, Pennsylvania, USA.
Pharm Res. 1996 May;13(5):794-7. doi: 10.1023/a:1016020221300.
To study the pharmacokinetics of SK&F 107647, a novel hematoregulatory agent, in rats, dogs, and patients with non-lymphoid solid tumor malignancy.
Sprague Dawley rats and beagle dogs (n = 6 each; 3 M, 3 F) were given 25 mg/kg of SK&F 107467 as an iv bolus injection, and patients (n = 6; 4 M, 2 F) received 100 mg/kg as a 2 hour iv infusion. Plasma samples were assayed for drug using either HPLC (rat and dog) or RIA (human).
In each species the plasma clearance (CL) of SK&F 107647 was low in relation to hepatic blood flow, and the volume of distribution (Vd ss) was reflective of distribution to extracellular body water. The plasma CL in humans was near that of average glomerular filtration rate. Using allometric equations for interspecies scaling (Y = a.W(b)), body-weight normalized human pharmacokinetic data were reasonably predicted using either the body weight normalized rat or the dog data. The allometric exponents (b) for CL, Vd(ss), and T(1/2) of SK&F 107647 were 0.63, 0.94, and 0.29, respectively.
Use of a limited pool of available animal data allowed for reasonable predictions of human pharmacokinetics of SK&F 107647.
研究新型血液调节剂SK&F 107647在大鼠、犬及非淋巴细胞性实体瘤恶性肿瘤患者体内的药代动力学。
给Sprague Dawley大鼠和比格犬（每组n = 6；3只雄性，3只雌性）静脉推注25 mg/kg的SK&F 107467，给患者（n = 6；4名男性，2名女性）静脉输注100 mg/kg，持续2小时。使用高效液相色谱法（大鼠和犬）或放射免疫分析法（人类）测定血浆样本中的药物。
在每个物种中，SK&F 107647的血浆清除率（CL）相对于肝血流量较低，分布容积（Vd ss）反映了药物向细胞外体液的分布。人类的血浆CL接近平均肾小球滤过率。使用种间缩放的异速生长方程（Y = a.W(b)），无论是使用体重标准化的大鼠数据还是犬数据，都能合理预测体重标准化的人类药代动力学数据。SK&F 107647的CL、Vd(ss)和T(1/2)的异速生长指数（b）分别为0.63、0.94和0.29。
使用有限的可用动物数据能够合理预测SK&F 107647的人体药代动力学。
