Bertilsson L, Braithwaite R, Tybring G, Garle M, Borgå O
Clin Pharmacol Ther. 1979 Aug;26(2):265-71. doi: 10.1002/cpt1979262265.
The cerebrospinal fluid (CSF) and plasma levels of demethylchlorimipramine (DMCI) were determined during treatment of depression or obsessive-compulsive disorders with chlorimipramine. In 18 patients the mean CSF/plasma ratio of DMCI was 2.6% +/- 0.7 SD with fourfold variation (1.1% to 4.0%). In spite of this variation, the levels in CSF and plasma at steady state correlated closely (r = 0.91; p less than 0.001). With equilibrium dialysis for the determination of the protein binding of DMCI, a much higher free fraction was found in patients (8.0 +/- 1.6%) and in control subjects (8.2 +/- 1.4%). It was shown that part of the plasma binding capacity was lost during the incubation. Results obtained by ultrafiltration (3.9 +/- 1.0% unbound drug) were closer to the in vivo results, but this method also had disadvantages; much of the drug was absorbed on the ultrafiltration dialysis membrane. Our results suggest that there is a need for care in the selection of a technique for studies of drug protein binding.
在使用氯米帕明治疗抑郁症或强迫症期间，测定了去甲氯米帕明（DMCI）的脑脊液（CSF）和血浆水平。18例患者中，DMCI的脑脊液/血浆平均比值为2.6%±0.7标准差，有四倍的变化范围（1.1%至4.0%）。尽管存在这种变化，但稳态时脑脊液和血浆中的水平密切相关（r = 0.91；p < 0.001）。采用平衡透析法测定DMCI的蛋白结合情况时，发现患者（8.0±1.6%）和对照受试者（8.2±1.4%）的游离分数要高得多。结果表明，在孵育过程中部分血浆结合能力丧失。通过超滤法得到的结果（未结合药物为3.9±1.0%）更接近体内结果，但该方法也有缺点；许多药物被超滤透析膜吸附。我们的结果表明，在选择药物蛋白结合研究技术时需要谨慎。
