Department of Drug Metabolism and Pharmacokinetics, Theravance, Inc., 901 Gateway Boulevard, South San Francisco, CA 94080, USA.
Antimicrob Agents Chemother. 2010 Aug;54(8):3365-71. doi: 10.1128/AAC.01750-09. Epub 2010 Jun 1.
The mass balance and pharmacokinetics of telavancin, a semisynthetic lipoglycopeptide antimicrobial agent, were characterized in an open-label, phase 1 study of six healthy male subjects. After a single 1-h intravenous infusion of 10 mg/kg [14C]telavancin (0.68 microCi/kg), blood, urine, and feces were collected at regular intervals up to 216 h postdose. Whole blood, plasma, urine, and fecal samples were assayed for total radioactivity using scintillation counting; plasma and urine were also assayed for parent drug and metabolites using liquid chromatography with tandem mass spectrometry. The concentration-time profiles for telavancin and total radioactivity in plasma were comparable from 0 to 24 h after the study drug administration. Telavancin accounted for >95% and 83% of total radioactivity in plasma at 12 h and 24 h, respectively. By 216 h, approximately 76% of the total administered dose was recovered in urine while only 1% was collected in feces. Unchanged telavancin accounted for most (83%) of the eliminated dose. Telavancin metabolite THRX-651540 along with two other hydroxylated metabolites (designated M1 and M2) accounted for the remaining radioactivity recovered from urine. The mean concentrations of total radioactivity in whole blood were lower than the concentration observed in plasma, and mean concentrations of THRX-651540 in plasma were minimal relative to mean plasma telavancin concentrations. These observations demonstrate that most of an administered telavancin dose is eliminated unchanged via the kidneys. Intravenous telavancin at 10 mg/kg was well tolerated by all subjects.
在一项开放标签、单剂量 1 期临床试验中，6 名健康男性受试者接受了单次 1 小时静脉输注 10mg/kg[14C]替拉万星（0.68 微居里/千克）。在给药后 216 小时内，定期采集血、尿和粪便样本。使用闪烁计数法对全血、血浆、尿液和粪便样本进行总放射性检测；使用液相色谱-串联质谱法对血浆和尿液中的母体药物和代谢物进行检测。研究药物给药后 0 至 24 小时，替拉万星和血浆中总放射性的浓度-时间曲线相似。在 12 小时和 24 小时时，替拉万星分别占血浆中总放射性的>95%和 83%。至 216 小时，约 76%的给药剂量以原形经尿液排泄，而仅有 1%从粪便中收集。未改变的替拉万星占消除剂量的大部分（83%）。替拉万星代谢物 THRX-651540 以及另外两种羟化代谢物（命名为 M1 和 M2）占尿液中回收放射性的其余部分。全血中总放射性的平均浓度低于血浆中的浓度，而血浆中 THRX-651540 的平均浓度相对于平均血浆替拉万星浓度最小。这些观察结果表明，大多数给予的替拉万星剂量通过肾脏以原形消除。所有受试者均能耐受 10mg/kg 的替拉万星静脉注射。
