Bonati M, Kanto J, Tognoni G
Clin Pharmacokinet. 1982 Jul-Aug;7(4):312-35. doi: 10.2165/00003088-198207040-00003.
The distribution of drugs into the cerebrospinal fluid has long been considered a challenging field of investigation in 2 major respects: (a) understanding how the physicochemical properties (molecular weight, pKa, plasma protein binding) of various molecules influence their movements across such a specific structure as the blood-brain barrier; and (b) defining the relationship between cerebrospinal fluid concentrations of various drugs and their central (side) effects. An attempt has been made to review the very dispersed information presently available to offer a clinically orientated picture of this area of pharmacokinetics. Drugs acting on the central nervous system (benzodiazepines, tricyclic antidepressants, anticonvulsants, opioids), antibacterial agents, cardiovascular drugs (beta-adrenoceptor blockers and digoxin), antineoplastic drugs (mainly methotrexate), and other miscellaneous agents (corticosteroids, cimetidine, methylxanthines) are reviewed. The available evidence seems to support the conclusion that only for methotrexate and antibacterial agents does knowledge of cerebrospinal fluid pharmacokinetics have direct therapeutic implications, while the mosaic of information available for other drugs does little more than provide a partially satisfactory picture.
长期以来，药物向脑脊液中的分布在两个主要方面一直被视为一个具有挑战性的研究领域：（a）了解各种分子的物理化学性质（分子量、pKa、血浆蛋白结合率）如何影响它们穿过血脑屏障这种特定结构的运动；（b）确定各种药物的脑脊液浓度与其中枢（副作用）效应之间的关系。本文试图对目前可得的非常分散的信息进行综述，以提供该药代动力学领域以临床为导向的概况。本文对作用于中枢神经系统的药物（苯二氮䓬类、三环类抗抑郁药、抗惊厥药、阿片类药物）、抗菌药物、心血管药物（β肾上腺素受体阻滞剂和地高辛）、抗肿瘤药物（主要是甲氨蝶呤）以及其他各类药物（皮质类固醇、西咪替丁、甲基黄嘌呤）进行了综述。现有证据似乎支持这样的结论：只有对于甲氨蝶呤和抗菌药物，脑脊液药代动力学知识具有直接的治疗意义，而关于其他药物的零散信息只不过提供了一个部分令人满意的情况。
