Zito R A, Reid P R
J Clin Pharmacol. 1981 Feb-Mar;21(2):100-5. doi: 10.1002/j.1552-4604.1981.tb01757.x.
Lidocaine plasma levels and indocyanine green clearance were measured in five normal volunteers and eight patients admitted to the coronary care unit. All individuals received lidocaine as a 1 mg/kg bolus and a 35 microgram/kg/min constant infusion for 180 minutes. Eight of the 13 (62 per cent) individuals studied (all normal volunteers and three patients) developed early, potentially subtherapeutic plasma lidocaine levels (less than or equal to 2.4 microgram/ml) within 15 minutes after starting therapy. Those individuals with subtherapeutic levels had either minimal (American Heart Association Class) or no clinical evidence of congestive heart failure. The use of indocyanine green (ICG) clearance as an estimate of hepatic plasma flow showed that individuals with early, subtherapeutic lidocaine levels had higher ICG clearance (9.33 +/- 0.32 ml/min . kg versus 2.90 +/- 1.74 ml/min . kg) and shorter ICG t 1/2 (2.02 +/- 0.99 minutes versus 3.6 +/- 0.69 minutes) and larger volume of distribution (36.1 +/- 16.3 ml/kg versus 19.5 +/- 12.8 ml/kg) than patients without subtherapeutic levels. This study suggests that early lidocaine kinetics may be significantly altered by clinical conditions that alter hepatic blood flow. The reappearance of arrhythmias shortly after initiating lidocaine therapy in patients without heart failure may be due to rapid hepatic clearance and subtherapeutic blood levels rather than lidocaine-resistant arrhythmias.
对5名正常志愿者和8名入住冠心病监护病房的患者测定了利多卡因血浆水平和吲哚菁绿清除率。所有个体均接受了1mg/kg的利多卡因静脉推注,并以35μg/kg/min的速度持续输注180分钟。在研究的13名个体中,有8名(62%)(全部为正常志愿者和3名患者)在开始治疗后15分钟内出现早期、可能低于治疗浓度的血浆利多卡因水平(小于或等于2.4μg/ml)。那些血浆水平低于治疗浓度的个体,要么有轻微的(美国心脏协会分级),要么没有充血性心力衰竭的临床证据。使用吲哚菁绿(ICG)清除率来估计肝血浆流量显示,早期血浆利多卡因水平低于治疗浓度的个体,其ICG清除率更高(9.33±0.32ml/min·kg,而2.90±1.74ml/min·kg),ICG半衰期更短(2.02±0.99分钟,而3.6±0.69分钟),分布容积更大(36.1±16.3ml/kg,而19.5±12.8ml/kg)。这项研究表明,早期利多卡因动力学可能会因改变肝血流量的临床状况而发生显著改变。在没有心力衰竭的患者中,利多卡因治疗开始后不久心律失常再次出现,可能是由于肝脏快速清除和血药浓度低于治疗浓度,而不是利多卡因抵抗性心律失常。