奎尼丁的药物及其代谢物的三个人。
文章的细节
-
引用
复制到剪贴板 -
Rakhit A Holford NH Guentert TW,马宏升K, Riegelman年代
奎尼丁的药物及其代谢物的三个人。
J Pharmacokinet Biopharm。1984年2月,12 (1):21。doi: 10.1007 / BF01063608。
- PubMed ID
-
6747817 (在PubMed]
- 文摘
-
奎尼丁的配置参数和三个的新陈代谢,3-hydroxy奎尼丁、奎尼丁N-oxide,和奎尼丁10,11-dihydrodiol,测定5正常健康志愿者经过长时间静脉输液和多个口服剂量。单个代谢物7小时后的血浆浓度恒定奎尼丁注入等离子奎尼丁水平为2.9 + / - 0.3 mg / L (SD): 3-hydroxy奎尼丁,0.32 + / - 0.06 mg / L;奎尼丁N-oxide, 0.28 + / - 0.03 mg / L;11-dihydrodiol和奎尼丁10日,0.13 + / - 0.04 mg / L。12后等离子体槽水平口服剂量的硫酸奎尼丁平均每4小时:奎尼丁,2.89 + / - 0.50 mg / L;3-hydroxy奎尼丁,0.83 + / - 0.36 mg / L;奎尼丁N-oxide, 0.40 + / - 0.13 mg / L;11-dihydrodiol和奎尼丁10日,0.38 + / - 0.08 mg / L。相对较高的等离子体浓度3-hydroxy奎尼丁代谢物在口服给药可能反映这个奎尼丁代谢物的初步形成。奎尼丁的两舱制模型为每个描述的代谢物和单舱模型血浆浓度时间曲线对静脉输液输液和多个口服剂量。 Mean (+/- SD) disposition parameters for quinidine from individual fits, after i.v. infusion were as follows: Vl, 0.37 +/- 0.09 L/kg; lambda 1, 0.094 +/- 0.009 min-1; lambda 2, 0.0015 +/- 0.0002 min-1; EX2, 0.013 +/- 0.002 min-1; clearance (ClQ), 3.86 +/- 0.83 ml/min/kg. Both plasma and urinary data were used to determine metabolic disposition parameters. Mean (+/- SD) values for the metabolites after i.v. quinidine infusion were as follows: 3-hydroxy quinidine: formation rate constant kmf, 0.0012 +/- 0.0005 min-1, volume of distribution, Vm, 0.99 +/- 0.47 L/kg; and elimination rate constant, kmu 0.0030 +/- 0.0002 min-1. Quinidine N-oxide: kmf, 0.00012 +/- 0.00003 min-1; Vm, 0.068 +/- 0.020 L/kg; and kmu, 0.0063 +/- 0.0008 min-1. Quinidine 10,11-dihydrodiol: kmf, 0.0003 +/- 0.0001 min-1; Vm, 0.43 +/- 0.29 L/kg; and kmu, 0.0059 +/- 0.0010 min-1. Oral absorption of quinidine was described by a zero order process with a bioavailability of 0.78. Concentration dependent renal elimination of 3-hydroxy quinidine was observed in two out of five subjects studied.
