Ochs H R, Schuppan U, Greenblatt D J, Abernethy D R
J Cardiovasc Pharmacol. 1983 Jul-Aug;5(4):697-9. doi: 10.1097/00005344-198307000-00027.
Acetaminophen is a widely prescribed analgesic/antipyretic metabolized by hepatic glucuronide and sulfate conjugation. Twelve patients, 30-66 years of age, with stable Class III or IV congestive heart failure (CHF) and 12 healthy controls matched for age, sex, and weight received single 650-mg intravenous doses of acetaminophen. Pharmacokinetic variables were determined from multiple plasma acetaminophen concentrations measured by liquid chromatography during 12 h after the dose. Compared with controls, mean total clearance of acetaminophen was reduced in CHF patients (3.56 vs. 4.59 ml/min/kg, p less than 0.025), indicating reduced biotransformation capacity in this disease. Volume of distribution was also significantly reduced in CHF patients (0.85 vs. 1.02 L/kg, p less than 0.05). Since elimination half-life depends on both volume of distribution and clearance (both of which were reduced), the half-life was similar between groups (2.87 vs. 2.34 h, NS). Thus, hepatic conjugation of acetaminophen is impaired in CHF. The finding may also apply to other drugs biotransformed by conjugation.
对乙酰氨基酚是一种广泛应用的镇痛/解热药物，通过肝脏葡萄糖醛酸化和硫酸化结合进行代谢。12例年龄在30 - 66岁之间、患有稳定的Ⅲ级或Ⅳ级充血性心力衰竭（CHF）的患者以及12名年龄、性别和体重相匹配的健康对照者接受了单次650毫克静脉注射对乙酰氨基酚。通过液相色谱法在给药后12小时内多次测量血浆对乙酰氨基酚浓度来确定药代动力学变量。与对照组相比，CHF患者对乙酰氨基酚的平均总清除率降低（3.56对4.59毫升/分钟/千克，p < 0.025），表明该疾病中生物转化能力降低。CHF患者的分布容积也显著降低（0.85对1.02升/千克，p < 0.05）。由于消除半衰期取决于分布容积和清除率（两者均降低），两组之间的半衰期相似（2.87对2.34小时，无显著性差异）。因此，CHF患者中对乙酰氨基酚的肝脏结合受损。这一发现可能也适用于其他通过结合进行生物转化的药物。
