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CSF and plasma levels of nortriptyline and its 10‐hydroxy metabolite.
Author(s) -
Nordin C.,
Bertilsson L.,
Siwers B.
Publication year - 1985
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1985.tb05086.x
Subject(s) - nortriptyline , metabolite , chemistry , endocrinology , active metabolite , medicine , pharmacokinetics , cerebrospinal fluid , muscarinic acetylcholine receptor , plasma concentration , pharmacology , anticholinergic , receptor , biochemistry , amitriptyline
After 3 weeks' nortriptyline (NT) treatment the mean plasma concentration of its 10‐hydroxy metabolite (10‐OH‐NT) (599 +/‐ 207 nmol l‐1) was higher than that of the parent drug (433 +/‐ 199 nmol l‐1) in 25 depressed patients. Also in the cerebrospinal fluid (CSF) the mean level of 10‐OH‐NT (67 +/‐ 20 nmol l‐1) was higher than that of NT (39 +/‐ 23 nmol l‐1). There was a strong correlation (P less than 0.001) between the CSF and plasma concentration of both NT (r = 0.92) and 10‐ OH‐NT (r = 0.77). The interindividual variation in the CSF/plasma ratio of both compounds was small, compared to the variation in plasma levels. These results show that 10‐OH‐NT passes the blood‐brain barrier as it is present in concentrations higher than those of NT in the CSF. 10‐OH‐NT has previously been shown to be a potent blocker of noradrenaline uptake and to have much less affinity for muscarinic receptors than NT itself. This active metabolite might therefore be a potential antidepressant with less disturbing anticholinergic side‐ effects.