THE USE OF PROBENECID FOR INCREASING PENICILLIN CONCENTRATIONS IN CEREBROSPINAL FLUID
THE USE OF PROBENECID FOR INCREASING PENICILLIN CONCENTRATIONS IN CEREBROSPINAL FLUID
复制标题
使用丙磺舒提高脑脊液中青霉素浓度
DOI：
10.1111/j.1600-0404.1969.tb01237.x
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发表时间：
1969
影响因子：
3.5
通讯作者：
K. Dewhurst
中科院分区：
文献类型：
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作者：
K. Dewhurst
人们早就认识到，青霉素只能以低浓度进入脑脊液（c.s.f.） （Fleming 1943, Floreg 1943, Rammelkamp h Keefer 1943）：事实上，Smith（1951）未能在实质性神经梅毒的“标准治疗方案”患者中检测到任何青霉素。Fishman（1966）在狗和大鼠的一系列实验中表明，probenecid是青霉素活性c.s.f.运输的最有效抑制剂。他指出，如果它在以下阶段增加c.s.f.浓度：(1)血清青霉素水平增加，(2)青霉素从c.s.f.到血清的主动运输被抑制，(3)随着probenecid与它竞争蛋白质结合，弥散性青霉素增加。Fishman发现，probenecid导致青霉素进入c.s.f.的比率“显著增加”，并使c.s.f.f.血浆滤液比率在一些狗中从4.1%提高到6.5%，在其他狗中从7.9%提高到10.9%。他得出的结论是：“当给每只狗服用丙戊酸时，c.s.f.中青霉素的绝对浓度更高”。在人类中，probenecid通过抑制肾小管分泌来增加血清和c.s.f.r西林浓度，并且在不确定的时间内耐受性良好（Nichols, Richards & Finland 1952, Gutman 1966）。2克口服probenecid可使血清甲氧西林增加2 - 3倍，并持续8小时（Henderson, Carleton h Hamburger, 1962）；血清青霉素浓度增加10倍（Martindale 1967）。
I t has long been recognized that penicillin penetrates into the cercbro-spinal fluid (C. S. F.) only in low concentrations, (Fleming 1943, Floreg 1943, Rammelkamp h Keefer 1943): Indeed Smith (1951) failed to detect any in patients having “the standard scheme of treatment” for parenchymatous neurosyphilis. In a series of experiments on dogs and rats, Fishman (1966) has shown that probenecid is the most effective inhibitor of the active C. S. F. transport of penicillin. He states that i t increases C. S. F. concentrations in the following stages: (1) serum penicillin levels are increased, (2 ) active transport of penicillin from the C. S. F. to the serum is inhibited, (3) there is an increase in diffusible penicillin as probenecid competes with i t for protein binding. Fishman found that probenecid caused a “marked increase” in the rate of entry of penicillin into the C. S. F., and raised C. S. FJplasma filtrate ratio from 4.1 per cent to 6.5 per cent in some dogs, and from 7.9 per cent to 10.9 per cent in others. He concluded that the “absolute concentration of penicillin in the C. S. F. was higher in each dog when probenecid was also given”. In man probenecid increases serum and C. S. F. penicillin concentrations by inhibiting renal tubular secretion and is well tolerated for an indefinite period (Nichols, Richards & Finland 1952, and Gutman 1966). Two grams of oral probenecid has been found to cause a two-threefold increase in serum methicillin persisting for 8 hours (Henderson, Carleton h Hamburger 1962); and a tenfold increase in serum penicillin concentration (Martindale 1967).