STEREOSELECTIVE EFFLUX OF (E)-10-HYDROXYNORTRIPTYLINE ENANTIOMERS FROM THE CEREBROSPINAL-FLUID OF DEPRESSED-PATIENTS

被引:13
作者
BERTILSSON, L
OTANI, K
DAHL, ML
NORDIN, C
ABERGWISTEDT, A
机构
[1] KAROLINSKA INST,HUDDINGE HOSP,DEPT PSYCHIAT,S-14186 HUDDINGE,SWEDEN
[2] KAROLINSKA INST,DANDERYDS HOSP,DEPT PSYCHIAT,S-18288 DANDERYD,SWEDEN
来源
PHARMACOLOGY & TOXICOLOGY | 1991年 / 68卷 / 02期
关键词
D O I
10.1111/j.1600-0773.1991.tb02044.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In 5 patients treated with nortriptyline or amitriptyline for at least 9 months, the cerebrospinal fluid (CSF)/plasma ratio for 10-hydroxynortriptyline (10-OH-NT) ranged from 0.085 to 0.172, which is similar to the ratio previously measured in patients treated for 3 weeks. In 4 other patients treated with racemic (E)-10-OH-NT, the mean concentration ratio between (-)- and (+)-(E)-10-OH-NT was 3.56 in plasma, 2.39 in plasma ultrafiltrate and 1.42 in CSF (one-way ANOVA; P < 0.001). The mean free fraction in plasma determined by ultrafiltration for (-)-(E)-10-OH-NT was 28.9 +/- S.D.1.1% and for the (+)-enantiomer 43.7 +/- 0.8% (P < 0.001) confirming the difference in protein binding shown previously in healthy subjects. There was a correlation between the concentration of 10-OH-NT (sum of enantiomers) in CSF and plasma ultrafiltrate (r = 0.96; n = 7; P < 0.001). The concentration in CSF was, however, only about 50% of that in the plasma ultrafiltrate and this seems to be due to a stereoselective transport of (E)-10-OH-NT out from the CSF. The secretion from the CSF is more pronounced for the (-)-compared to the (+)-enantiomer, which is consistent with the stereoselectivity of the renal secretion of these compounds.
引用
收藏
页码:100 / 103
页数:4
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