Gepts E, Sonck W A, Camu F, Vercruysse A
Eur J Anaesthesiol. 1987 Jan;4(1):35-43.
The pharmacokinetics of meptazinol (3 mg kg-1 i.v.), a centrally acting opioid agonist-antagonist, were studied in six male and six female patients during anaesthesia with 1-3 vol.% enflurane and an infusion of 10-30 micrograms kg-1 min-1 etomidate. Arterial blood samples were taken up to 300 min postinjection. The plasma meptazinol concentrations, determined by HPLC, best fitted to a three-compartment open mamillary model with central elimination using a non-linear extended least-squares regression analysis. Derived pharmacokinetic parameters indicated a rapid distribution (T1/2 pi = 1.24 +/- 0.83 min, T1/2 alpha = 7.55 +/- 3.97 min), a short elimination half-life (T1/2 beta = 86.9 +/- 15.6 min), a volume of the central compartment twice as large in females (Vc = 0.557 +/- 0.237 l kg-1) as in males (Vc = 0.274 +/- 0.144 l kg-1), a small distribution volume at steady state (Vss = 2.52 +/- 0.66 l kg-1) and a high total plasma clearance (ClP = 1547 +/- 385 ml min-1). The elimination rate microconstant in females (k10 = 0.0577 +/- 0.0337 min-1) was significantly lower than in males (k10 = 0.1093 +/- 0.0437 min-1 with a lower drug fraction in the central compartment in the post-distributive phase (Fc = males: 0.08 +/- 0.02, females 0.19 +/- 0.11). As Vss and ClP were similar in both groups, sex-related differences were only observed in the dynamics of distribution of the drug. From a pharmacokinetic point of view we suspect that meptazinol shows very little cumulation on repeated i.v. administration as necessary during anaesthesia.
在使用1 - 3体积%的安氟醚麻醉并输注10 - 30微克/千克/分钟依托咪酯的过程中，对6名男性和6名女性患者研究了中枢作用的阿片类激动 - 拮抗剂美普他酚（静脉注射3毫克/千克）的药代动力学。注射后长达300分钟采集动脉血样。通过高效液相色谱法测定的血浆美普他酚浓度，使用非线性扩展最小二乘回归分析，最符合具有中央消除的三室开放乳头模型。导出的药代动力学参数表明分布迅速（T1/2π = 1.24 ± 0.83分钟，T1/2α = 7.55 ± 3.97分钟），消除半衰期短（T1/2β = 86.9 ± 15.6分钟），女性中央室容积是男性的两倍（Vc = 0.557 ± 0.237升/千克对Vc = 0.274 ± 0.144升/千克），稳态分布容积小（Vss = 2.52 ± 0.66升/千克），总血浆清除率高（ClP = 1547 ± 385毫升/分钟）。女性的消除速率微常数（k10 = 0.0577 ± 0.0337分钟-1）显著低于男性（k10 = 0.1093 ± 0.04,37分钟-1），在分布后相中中央室药物分数较低（Fc = 男性：0.08 ± 0.02，女性0.19 ± 0.11）。由于两组的Vss和ClP相似，仅在药物分布动力学方面观察到性别相关差异。从药代动力学角度来看，我们怀疑美普他酚在麻醉期间重复静脉给药时几乎没有蓄积。
