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Stereoselective efflux of (E)-10-hydroxynortriptyline enantiomers from the cerebrospinal fluid of depressed patients.
- Source :
-
Pharmacology & toxicology [Pharmacol Toxicol] 1991 Feb; Vol. 68 (2), pp. 100-3. - Publication Year :
- 1991
-
Abstract
- 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 less than 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 less than 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 less than 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.
Details
- Language :
- English
- ISSN :
- 0901-9928
- Volume :
- 68
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Pharmacology & toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 1852713
- Full Text :
- https://doi.org/10.1111/j.1600-0773.1991.tb02044.x