Cohen O, Zylber-Katz E, Caraco Y, Granit L, Levy M
Department of Medicine, Hadassah University Hospital, Jerusalem, Israel.
Eur J Clin Pharmacol. 1998 Sep;54(7):549-53. doi: 10.1007/s002280050511.
Dipyrone is a veteran analgesic and antipyretic drug. After oral administration it is rapidly converted by hydrolysis to 4-methylaminoantipyrine (MAA), which is further metabolized to 4-formylaminoantipyrine (FAA), 4-aminoantipyrine (AA) and 4-acetylaminoantipyrine (AAA). It is still debated whether the site of dipyrone action is in the central nervous system or in the periphery. The purpose of this study was to assess whether dipyrone metabolites cross the blood-brain barrier (BBB) when administered systemically.
Twenty-eight patients undergoing diagnostic lumbar puncture (LP) were randomly assigned to receive two 0.5-g dipyrone tablets either 30 min, 1, 1.5, 2, 4, 6, 8 h or 12 h before the lumbar tap. A 5-ml blood sample was drawn concomitantly.
All four metabolites were found in the cerebrospinal fluid (CSF). Their appearance in the CSF lagged but followed that found in the plasma. Mean CSF/plasma ratios were 0.40 (for samples taken between 0.5-2 h) and 0.83 (for samples taken between 4-12 h) for MAA, 0.62 for AA, 0.55 for FAA and 0.40 for AAA (for all samples). Significant correlation was found between plasma and CSF concentrations for MAA, AA, FAA and AAA.
The concentration-time course of dipyrone metabolite CSF concentrations are in agreement with that of their plasma concentrations and the analgesic effect of dipyrone.
安乃近是一种老牌的解热镇痛药。口服后，它会通过水解迅速转化为4-甲基氨基安替比林（MAA），MAA会进一步代谢为4-甲酰氨基安替比林（FAA）、4-氨基安替比林（AA）和4-乙酰氨基安替比林（AAA）。安乃近的作用部位是在中枢神经系统还是在外周，目前仍存在争议。本研究的目的是评估全身给药时安乃近代谢产物是否能穿过血脑屏障（BBB）。
28例行诊断性腰椎穿刺（LP）的患者被随机分配，在腰穿前30分钟、1小时、1.5小时、2小时、4小时、6小时、8小时或12小时服用两片0.5克的安乃近片。同时采集5毫升血样。
在脑脊液（CSF）中发现了所有四种代谢产物。它们在脑脊液中的出现滞后于但跟随血浆中的情况。MAA的脑脊液/血浆平均比值在0.5 - 2小时采集的样本中为0.40，在4 - 12小时采集的样本中为0.83；AA为0.62，FAA为0.55，AAA为0.40（所有样本）。MAA、AA、FAA和AAA的血浆浓度与脑脊液浓度之间存在显著相关性。
安乃近代谢产物在脑脊液中的浓度-时间过程与其血浆浓度以及安乃近的镇痛效果一致。
