Rocci M L, Vlasses P H, Lener M E, Fruncillo R A, Sirgo M A
Division of Clinical Pharmacology, Jefferson Medical College, Philadelphia, PA.
J Clin Pharmacol. 1989 Oct;29(10):891-5. doi: 10.1002/j.1552-4604.1989.tb03250.x.
The effects of labetalol, diltiazem and verapamil on antipyrine and indocyanine green clearance were evaluated in a placebo-controlled, repeated measures evaluation. Twelve healthy subjects received either labetalol (200 mg every 12 hours), diltiazem (90 mg. every 8 hours), verapamil (80 mg every 8 hours), or placebo (every 12 hours) for 4 days. On the morning of Day 3 immediately following their dose, the subjects assumed the supine position for 90 minutes, after which time a 0.5 mg/kg dose of indocyanine green was administered. Blood samples were obtained serially over a 20 minutes period for indocyanine green plasma concentration determinations by HPLC. Ten minutes later, subjects ingested a 1.2 Gm. dose of antipyrine and blood samples were obtained over a 48 hour period for antipyrine plasma concentration determinations by HPLC. A 2 week washout period separated treatment sequences. Mean (SD) antipyrine clearance (L/hr/kg) following diltiazem [0.028 (0.010)] and verapamil [0.030 (0.012)] treatment was significantly lower than that observed following placebo [0.039 (0.012)]. Antipyrine clearance following labetalol administration [0.033 (0.010)] was not significantly different from that observed following placebo, diltiazem or verapamil administration. No effects of these drugs on indocyanine green clearance could be detected.
在一项安慰剂对照的重复测量评估中,对拉贝洛尔、地尔硫䓬和维拉帕米对安替比林和吲哚菁绿清除率的影响进行了评估。12名健康受试者接受拉贝洛尔(每12小时200毫克)、地尔硫䓬(每8小时90毫克)、维拉帕米(每8小时80毫克)或安慰剂(每12小时)治疗4天。在第3天早晨给药后,受试者立即仰卧90分钟,之后给予0.5毫克/千克剂量的吲哚菁绿。在20分钟内连续采集血样,通过高效液相色谱法测定吲哚菁绿血浆浓度。10分钟后,受试者摄入1.2克剂量的安替比林,并在48小时内采集血样,通过高效液相色谱法测定安替比林血浆浓度。两个治疗序列之间有2周的洗脱期。地尔硫䓬[0.028(0.010)]和维拉帕米[0.030(0.012)]治疗后的平均(标准差)安替比林清除率(升/小时/千克)显著低于安慰剂组[0.039(0.012)]。拉贝洛尔给药后的安替比林清除率[0.033(0.010)]与安慰剂、地尔硫䓬或维拉帕米给药后的清除率无显著差异。未检测到这些药物对吲哚菁绿清除率有影响。