Gremse D A, Fillingim E, Hoff C J, Wells D J, Boerth R C
Department of Pediatrics, University of South Alabama College of Medicine, Mobile, Alabama 36640-0130, USA.
J Pediatr. 1998 Jun;132(6):989-93. doi: 10.1016/s0022-3476(98)70396-8.
To evaluate hepatic drug metabolism, as determined by the formation of monoethylglycinexylidide (MEGX) after lidocaine injection and indocyanine green (ICG) clearance, in patients with sickle cell disease.
A case-control study including 19 patients with homozygous hemoglobin S, and 13 age- and sex-matched black control subjects. Serum MEGX concentration was measured after intravenous injection of 1 mg/kg (maximum 50 mg) lidocaine. ICG (0.5 mg/kg) was injected concomitantly and absorbance (805 nm) of serum was measured over time to determine its volume of distribution, serum half-life, and hepatic blood flow.
MEGX formation at 15 minutes was decreased in patients with sickle cell disease compared with formation in the control subjects (39.9 +/- 18.0 vs 65.6 +/- 50.0 micrograms/L, respectively, p < 0.02). The volume of distribution of ICG was increased in patients with sickle cell disease compared with that in the control subjects (0.21 +/- 0.09 vs 0.11 +/- 0.03 L/kg, p < 0.01). This partly accounts for the decreased MEGX formation. The ICG half-life was similar in both groups (3.8 +/- 1.5 vs 3.1 +/- 1.0 min). Hepatic blood flow, derived from ICG clearance, was increased in sickle cell patients compared with that of the control subjects (12.2 +/- 4.5 vs 8.1 +/- 2.1 ml/kg/min, p < 0.01).
Hepatic drug metabolism, as assessed by MEGX formation after lidocaine injection, is impaired in patients with sickle cell disease. This impairment may have clinical implications when using hepatically metabolized medications in patients with sickle cell disease.
通过注射利多卡因后单乙基甘氨酰二甲苯胺(MEGX)的生成及吲哚菁绿(ICG)清除率来评估镰状细胞病患者的肝脏药物代谢情况。
一项病例对照研究,纳入19例纯合血红蛋白S患者以及13例年龄和性别匹配的黑人对照者。静脉注射1mg/kg(最大50mg)利多卡因后测定血清MEGX浓度。同时注射ICG(0.5mg/kg),并随时间测量血清吸光度(805nm),以确定其分布容积、血清半衰期和肝血流量。
与对照组相比,镰状细胞病患者在15分钟时MEGX的生成减少(分别为39.9±18.0与65.6±50.0μg/L,p<0.02)。与对照组相比,镰状细胞病患者ICG的分布容积增加(0.21±0.09与0.11±0.03L/kg,p<0.01)。这部分解释了MEGX生成减少的原因。两组的ICG半衰期相似(3.8±1.5与3.1±1.0分钟)。与对照组相比,镰状细胞病患者由ICG清除率得出的肝血流量增加(12.2±4.5与8.1±2.1ml/kg/min,p<0.01)。
通过注射利多卡因后MEGX生成评估的肝脏药物代谢在镰状细胞病患者中受损。在镰状细胞病患者使用经肝脏代谢的药物时,这种损害可能具有临床意义。