Worboys Philip D, Wong Shekman L, Barriere Steven L
Theravance Biopharma US, Inc., 901 Gateway Boulevard, South San Francisco, CA, 94080, USA.
AbbVie Biotherapeutics Corp., Redwood City, CA, 94063, USA.
Eur J Clin Pharmacol. 2015 Jun;71(6):707-714. doi: 10.1007/s00228-015-1847-6. Epub 2015 May 5.
We evaluated the effect of renal impairment (RI) on the pharmacokinetics of telavancin and hydroxypropylbetadex (excipient in the telavancin drug product).
Adults with normal, mild, moderate or severe RI or end-stage renal disease (ESRD) receiving haemodialysis were included in two open-label, phase I studies of single-dose telavancin at 7.5 mg/kg (study A, n = 29) or 10 mg/kg (study B, n = 43). Pharmacokinetic analysis of telavancin and hydroxypropylbetadex plasma concentration versus time was performed in these subjects.
The results in studies A and B were similar: telavancin systemic exposure (area under the concentration-time curve from 0 to infinity [AUC0-∞]) increased with RI. Telavancin half-life (h, mean ± SD) increased in subjects with severe RI compared with subjects with normal renal function from 6.9 ± 0.6 in study A and 6.5 ± 0.9 in study B to 14.5 ± 1.3 and 11.8 ± 6.7, respectively. Conversely, clearance (ml/h/kg, mean ± SD) decreased in subjects with severe RI compared with subjects with normal renal function from 13.7 ± 2.1 in study A and 17.0 ± 3.2 in study B to 6.18 ± 0.63 and 6.5 ± 1.5, respectively. Systemic exposures for hydroxypropylbetadex also increased with severity of RI.
Results from two independent phase 1 studies suggest that dose adjustment of telavancin is required in subjects with varying degrees of RI.
我们评估了肾功能损害（RI）对特拉万星及羟丙基倍他环糊精（特拉万星药品中的辅料）药代动力学的影响。
两项单剂量特拉万星（7.5mg/kg，研究A，n = 29；或10mg/kg，研究B，n = 43）的开放标签I期研究纳入了具有正常、轻度、中度或重度RI或接受血液透析的终末期肾病（ESRD）的成年人。对这些受试者进行了特拉万星和羟丙基倍他环糊精血药浓度随时间变化的药代动力学分析。
研究A和B的结果相似：特拉万星的全身暴露量（浓度-时间曲线下从0至无穷大的面积[AUC0-∞]）随RI增加。与肾功能正常的受试者相比，重度RI受试者的特拉万星半衰期（小时，均值±标准差）增加，在研究A中从6.9±0.6增加至14.5±1.3，在研究B中从6.5±0.9增加至11.8±6.7。相反，与肾功能正常的受试者相比，重度RI受试者的清除率（ml/h/kg，均值±标准差）降低，在研究A中从13.7±2.1降至6.18±0.63，在研究B中从17.0±3.2降至6.5±1.5。羟丙基倍他环糊精的全身暴露量也随RI严重程度增加。
两项独立的I期研究结果表明，不同程度RI的受试者需要调整特拉万星的剂量。
