Entry of diazepam and its major matabolite into cerebrospinal fluid.
Entry of diazepam and its major matabolite into cerebrospinal fluid.
复制标题
地西泮及其主要代谢物进入脑脊液。
DOI：
10.1007/bf00432376
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发表时间：
1980
影响因子：
3.4
通讯作者：
Lloyd,BL
中科院分区：
文献类型：
--
作者：
Greenblatt,DJ;Ochs,HR;Lloyd,BL
五只狗接受单次 1.0 mg/kg 剂量的地西泮 (DZ) IV。在给药后长达 8 小时内，通过电子捕获气液色谱法同时测量血浆和脑池脑脊液 (CSF) 中 DZ 及其主要代谢物去甲基地西泮 (DMDZ) 的浓度。 DZ 迅速从血浆中消除（半衰期 0.3-1.3 小时）； DZ 的消失反映在 DMDZ 的形成上，而 DMDZ 又慢慢地被消除。 DZ 和 DMDZ 均快速渗透 CSF，并且 CSF 中的浓度与血浆中的浓度平行下降。尽管吸收速度很快，但 DZ 和 DMDZ 的脑脊液转移程度受到血浆蛋白结合的限制。平均CSF：DZ（范围0.023-0.137）和DMDZ（范围0.047-0.119）的血浆浓度比与血浆中未结合的分数高度相关（r分别=0.95和0.80）。因此，CSF 中的 DZ 和 DMDZ 浓度（推测反映了作用部位的浓度）是由未结合的血浆浓度确定的。药理作用的强度更可能与未结合的血浆浓度相关，而不是与总血浆浓度相关。
Five dogs received a single 1.0 mg/kg dose of diazepam (DZ) IV. Concentrations of DZ and its major metabolite desmethyldiazepam (DMDZ) were simultaneously measured in plasma and cisternal cerebrospinal fluid (CSF) for up to 8 h after the dose by electron-capture gas-liquid chromatography. DZ was rapidly eliminated from plasma (half-life 0.3–1.3 h); DZ disappearance was mirrored by formation of DMDZ, which in turn was eliminated slowly. Both DZ and DMDZ rapidly penetrated CSF and concentrations in CSF declined parallel with those in plasma. Despite rapid uptake, the extent of CSF transfer of DZ and DMDZ was limited by plasma protein binding. Mean CSF: plasma concentration ratios for DZ (range 0.023–0.137) and DMDZ (range 0.047–0.119) were highly correlated with the unbound fraction in plasma (r=0.95 and 0.80, respectively). Thus DZ and DMDZ concentrations in CSF, presumed to reflect concentrations at the site of action, are determined by unbound plasma concentrations. The intensity of pharmacologic action is more likely to correlate with unbound than with total plasma concentrations.