替地唑胺口服给药后的药代动力学:单次和多次给药，食物的作用，以及前药的两种固体形式的比较。
文章的细节
-
引用
复制到剪贴板 -
Flanagan SD, Bien PA, Munoz KA, Minassian SL, Prokocimer PG
替地唑胺口服给药后的药代动力学:单次和多次给药，食物的作用，以及前药的两种固体形式的比较。
2014年3月34日(3):240-50。doi: 10.1002 / phar.1337。Epub 2013年8月7日。
- PubMed ID
-
23926058 (PubMed视图］
- 摘要
-
目的:在口服磷酸替二唑二钠(TPD)后，研究了替二唑胺的单剂量和多剂量药代动力学(PK)，包括食物对PK的影响。测定了TPD与游离磷酸替二唑胺酸的相对生物利用度，以将这些研究结果和其他研究结果与进一步开发的前药固体形式联系起来。设计:随机安慰剂对照，双盲单次和多次上升剂量研究，随机开放标签，交叉食物效应和相对生物利用度研究。单位:临床研究单位。必威国际app参与者:健康受试者。干预措施:研究TR701-101招募了40名受试者单次上升剂量(200- 1200mg TPD或安慰剂)和40名受试者21天多次上升剂量(200,300或400mg TPD一次/天;利奈唑胺600 mg, 2次/日;或者安慰剂)。研究TR701-103是一项食物效应研究，12名受试者服用600 mg TPD。研究TR701-108是一项相对生物利用度研究，在12名受试者中给予150mg的替二唑等量TPD或磷酸替二唑。测量和主要结果:收集了前药磷酸替唑胺、其活性部分替唑胺和/或利奈唑胺的血药浓度。 After administration of 200 to 600 mg TPD, tedizolid values increased approximately dose proportionally in area under the concentration-time curve (AUC) and maximum plasma concentration (Cmax ). Tedizolid half-life values were approximately 2-fold greater compared with linezolid. TPD administration with food delayed tedizolid absorption and reduced Cmax relative to the fasted state but did not alter AUC. Minimal accumulation was predicted and observed for tedizolid, whereas observed accumulation of linezolid exceeded predictions based on single-dose PK. Comparable PK of tedizolid was observed following oral administration of either TPD or tedizolid phosphate. In the multiple-ascending dose study, 3 of 24 tedizolid subjects were withdrawn under prespecified stopping rules (one each of elevated alanine aminotransferase, low reticulocyte count, or low white blood cell count), as was 1 of 8 linezolid subjects (low reticulocyte count). CONCLUSIONS: Overall, tedizolid has a favorable PK profile, a half-life that supports once daily administration, and no nonlinearities at steady state. Tedizolid phosphate can be administered without regard to food.
引用本文的药物库数据
- 药物