Hartvig P, Pettersson E, Wiklund L, Lindström B
Department of Anesthesiology and Intensive Care, Uppsala University Hospital, Sweden.
J Clin Anesth. 1991 Mar-Apr;3(2):137-42. doi: 10.1016/0952-8180(91)90011-b.
To determine the effects of intravenous (IV) 9-amino-1,2,3,4-tetrahydroacridine (THA) on postoperative somnolence in comparison to its pharmacokinetics.
Open-label study of the pharmacokinetics and effects of THA.
Postoperative intensive care ward at the Department of Neurosurgery, Uppsala University Hospital, Sweden.
Ten neurosurgical patients immediately after their operations were given 30 mg of THA for reversal of postoperative somnolence.
Plasma concentrations of THA and, in seven cases, the metabolite 1-hydroxy-THA were assayed using high-performance liquid chromatography. The pharmacokinetic data were compared to the degree of sedation and pain relief. After an IV dose of 30 mg THA, plasma concentrations were fit to an open two- or three-compartment model.
The antagonistic effect of THA on sedation occurred immediately following IV administration and lasted 60 to 90 minutes. At a mean plasma THA concentration of 44 +/- 18 ng/ml, patients were resedated. There was no obvious relation between analgesia and plasma THA concentrations. Side effects such as nausea, salivation, and lower heart rate (HR) were observed in several patients. Plasma clearance (C1) was high and showed a twofold inter-individual variation, with a mean of 2.64 +/- 1.17 L/h. Volume of distribution (Vd gamma) varied between 300 and 850 liters, with a mean of 477 +/- 185 liters. The plasma half-lives of rapid and slow distribution, and elimination were 2.1 +/- 0.7 minutes, 26 +/- 18 minutes, and 133 +/- 48 minutes, respectively. Maximum plasma concentrations of 1-hydroxy-THA were 27 to 90 ng/ml in five patients; the concentration was below 1 ng/ml in two other patients.
The duration of the effects of THA as an antagonist of postoperative sedation was only about double that seen previously after the IV administration of physostigmine in a similar group of patients, although the elimination half-life of THA was six times longer than that of physostigmine. A larger dose of THA possibly could have been given to prolong the period of antagonism of sedation, but the profile of adverse effects seen even at the doses used precluded that option.
与9-氨基-1,2,3,4-四氢吖啶（THA）的药代动力学相比，确定静脉注射THA对术后嗜睡的影响。
THA药代动力学及效应的开放标签研究。
瑞典乌普萨拉大学医院神经外科术后重症监护病房。
10例神经外科手术患者术后立即给予30mg THA以逆转术后嗜睡。
采用高效液相色谱法测定THA的血浆浓度，7例患者还测定了代谢产物1-羟基-THA的血浆浓度。将药代动力学数据与镇静程度和疼痛缓解情况进行比较。静脉注射30mg THA后，血浆浓度拟合为开放二室或三室模型。
THA静脉注射后立即产生对抗镇静的作用，持续60至90分钟。血浆THA平均浓度为44±18ng/ml时，患者再次出现嗜睡。镇痛与血浆THA浓度之间无明显关系。部分患者出现恶心、流涎和心率降低等副作用。血浆清除率（C1）较高，个体间差异达两倍，平均为2.64±1.17L/h。分布容积（Vdγ）在300至850升之间，平均为477±185升。快速分布、缓慢分布和消除的血浆半衰期分别为2.1±0.7分钟、26±18分钟和133±48分钟。5例患者1-羟基-THA的最大血浆浓度为27至90ng/ml；另外2例患者该浓度低于1ng/ml。
THA作为术后镇静拮抗剂的作用持续时间仅约为先前在类似患者群体中静脉注射毒扁豆碱后观察到的两倍，尽管THA的消除半衰期比毒扁豆碱长6倍。可能给予更大剂量的THA以延长镇静拮抗作用时间，但即使在所用剂量下观察到的不良反应情况也排除了这种选择。
