Steady-state plasma levels of E- and Z-10-OH-nortriptyline in nortriptyline-treated patients

Significance of concurrent medication and the sparteine oxidation phenotype

Lars F. Gram*, Kim Brøsen, Per Kragh-Sørensen, Peder Christensen

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Steady-state plasma levels of nortriptyline and E- and Z-10-OH-nortriptyline were determined in 55 depressed patients during long-term treatment. Dose-corrected steady-state levels varied by a factor of 20 for nortriptyline, a factor of 7 for E-10-OH-nortriptyline (sum of enantiomers), and a factor of 12 for Z-10-OH-nortriptyline (sum of enantiomers). The E-10-OH-nortriptyline levels were higher than the corresponding nortriptyline levels in about 50% of the patients and the nortriptyline/E-10-OH-nortriptyline ratio ranged from 0.27 to 4.8. In contrast to E-10-OH-nortriptyline, the steadystate levels of Z-10-OH-nortriptyline correlated significantly with the nortriptyline levels (s = 0.68, n = 55, p < 0.001) and the nortriptyline/Z-10-OH-nortriptyline ratio ranged from 1.7 to 10. Patients on concurrent treatment with perphenazine or benzodiazepines had higher nortriptyline and nortriptyline/E-10-OH-nortriptyline ratios than patients taking lithium or no other psychotropic drugs. A sparteine test was carried out in 22 patients and the sparteine metabolic ratio correlated significantly with the dose-corrected steady-state levels of nortriptyline (rs = 0.62, p < 0.01) and E-10-OH-nortriptyline (rs = -0.52, p < 0.02) and particularly well with the ratio nortriptyline/E-10-OH-nortriptyline (rs = 0.83). The genetic variability in the sparteine/debrisoquine P-450 isozyme appeared to be clearly more important for the interindividual variation in 10-hydroxylation of nortriptyline than the possible interactions with concurrent medication.

OriginalsprogEngelsk
TidsskriftTherapeutic Drug Monitoring
Vol/bind11
Udgave nummer5
Sider (fra-til)508-514
Antal sider7
ISSN0163-4356
DOI
StatusUdgivet - 1. jan. 1989

Fingeraftryk

Nortriptyline

Citer dette

@article{0111be601fa3416ebc56f604c4436b73,
title = "Steady-state plasma levels of E- and Z-10-OH-nortriptyline in nortriptyline-treated patients: Significance of concurrent medication and the sparteine oxidation phenotype",
abstract = "Steady-state plasma levels of nortriptyline and E- and Z-10-OH-nortriptyline were determined in 55 depressed patients during long-term treatment. Dose-corrected steady-state levels varied by a factor of 20 for nortriptyline, a factor of 7 for E-10-OH-nortriptyline (sum of enantiomers), and a factor of 12 for Z-10-OH-nortriptyline (sum of enantiomers). The E-10-OH-nortriptyline levels were higher than the corresponding nortriptyline levels in about 50{\%} of the patients and the nortriptyline/E-10-OH-nortriptyline ratio ranged from 0.27 to 4.8. In contrast to E-10-OH-nortriptyline, the steadystate levels of Z-10-OH-nortriptyline correlated significantly with the nortriptyline levels (s = 0.68, n = 55, p < 0.001) and the nortriptyline/Z-10-OH-nortriptyline ratio ranged from 1.7 to 10. Patients on concurrent treatment with perphenazine or benzodiazepines had higher nortriptyline and nortriptyline/E-10-OH-nortriptyline ratios than patients taking lithium or no other psychotropic drugs. A sparteine test was carried out in 22 patients and the sparteine metabolic ratio correlated significantly with the dose-corrected steady-state levels of nortriptyline (rs = 0.62, p < 0.01) and E-10-OH-nortriptyline (rs = -0.52, p < 0.02) and particularly well with the ratio nortriptyline/E-10-OH-nortriptyline (rs = 0.83). The genetic variability in the sparteine/debrisoquine P-450 isozyme appeared to be clearly more important for the interindividual variation in 10-hydroxylation of nortriptyline than the possible interactions with concurrent medication.",
keywords = "Drug oxidation, Hydroxylation, Interaction, Nortriptyline, Sparteine/debrisoquine",
author = "Gram, {Lars F.} and Kim Br{\o}sen and Per Kragh-S{\o}rensen and Peder Christensen",
year = "1989",
month = "1",
day = "1",
doi = "10.1097/00007691-198909000-00003",
language = "English",
volume = "11",
pages = "508--514",
journal = "Therapeutic Drug Monitoring",
issn = "0163-4356",
publisher = "Lippincott Williams & Wilkins",
number = "5",

}

Steady-state plasma levels of E- and Z-10-OH-nortriptyline in nortriptyline-treated patients : Significance of concurrent medication and the sparteine oxidation phenotype. / Gram, Lars F.; Brøsen, Kim; Kragh-Sørensen, Per; Christensen, Peder.

I: Therapeutic Drug Monitoring, Bind 11, Nr. 5, 01.01.1989, s. 508-514.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Steady-state plasma levels of E- and Z-10-OH-nortriptyline in nortriptyline-treated patients

T2 - Significance of concurrent medication and the sparteine oxidation phenotype

AU - Gram, Lars F.

AU - Brøsen, Kim

AU - Kragh-Sørensen, Per

AU - Christensen, Peder

PY - 1989/1/1

Y1 - 1989/1/1

N2 - Steady-state plasma levels of nortriptyline and E- and Z-10-OH-nortriptyline were determined in 55 depressed patients during long-term treatment. Dose-corrected steady-state levels varied by a factor of 20 for nortriptyline, a factor of 7 for E-10-OH-nortriptyline (sum of enantiomers), and a factor of 12 for Z-10-OH-nortriptyline (sum of enantiomers). The E-10-OH-nortriptyline levels were higher than the corresponding nortriptyline levels in about 50% of the patients and the nortriptyline/E-10-OH-nortriptyline ratio ranged from 0.27 to 4.8. In contrast to E-10-OH-nortriptyline, the steadystate levels of Z-10-OH-nortriptyline correlated significantly with the nortriptyline levels (s = 0.68, n = 55, p < 0.001) and the nortriptyline/Z-10-OH-nortriptyline ratio ranged from 1.7 to 10. Patients on concurrent treatment with perphenazine or benzodiazepines had higher nortriptyline and nortriptyline/E-10-OH-nortriptyline ratios than patients taking lithium or no other psychotropic drugs. A sparteine test was carried out in 22 patients and the sparteine metabolic ratio correlated significantly with the dose-corrected steady-state levels of nortriptyline (rs = 0.62, p < 0.01) and E-10-OH-nortriptyline (rs = -0.52, p < 0.02) and particularly well with the ratio nortriptyline/E-10-OH-nortriptyline (rs = 0.83). The genetic variability in the sparteine/debrisoquine P-450 isozyme appeared to be clearly more important for the interindividual variation in 10-hydroxylation of nortriptyline than the possible interactions with concurrent medication.

AB - Steady-state plasma levels of nortriptyline and E- and Z-10-OH-nortriptyline were determined in 55 depressed patients during long-term treatment. Dose-corrected steady-state levels varied by a factor of 20 for nortriptyline, a factor of 7 for E-10-OH-nortriptyline (sum of enantiomers), and a factor of 12 for Z-10-OH-nortriptyline (sum of enantiomers). The E-10-OH-nortriptyline levels were higher than the corresponding nortriptyline levels in about 50% of the patients and the nortriptyline/E-10-OH-nortriptyline ratio ranged from 0.27 to 4.8. In contrast to E-10-OH-nortriptyline, the steadystate levels of Z-10-OH-nortriptyline correlated significantly with the nortriptyline levels (s = 0.68, n = 55, p < 0.001) and the nortriptyline/Z-10-OH-nortriptyline ratio ranged from 1.7 to 10. Patients on concurrent treatment with perphenazine or benzodiazepines had higher nortriptyline and nortriptyline/E-10-OH-nortriptyline ratios than patients taking lithium or no other psychotropic drugs. A sparteine test was carried out in 22 patients and the sparteine metabolic ratio correlated significantly with the dose-corrected steady-state levels of nortriptyline (rs = 0.62, p < 0.01) and E-10-OH-nortriptyline (rs = -0.52, p < 0.02) and particularly well with the ratio nortriptyline/E-10-OH-nortriptyline (rs = 0.83). The genetic variability in the sparteine/debrisoquine P-450 isozyme appeared to be clearly more important for the interindividual variation in 10-hydroxylation of nortriptyline than the possible interactions with concurrent medication.

KW - Drug oxidation

KW - Hydroxylation

KW - Interaction

KW - Nortriptyline

KW - Sparteine/debrisoquine

UR - http://www.scopus.com/inward/record.url?scp=0024465177&partnerID=8YFLogxK

U2 - 10.1097/00007691-198909000-00003

DO - 10.1097/00007691-198909000-00003

M3 - Journal article

VL - 11

SP - 508

EP - 514

JO - Therapeutic Drug Monitoring

JF - Therapeutic Drug Monitoring

SN - 0163-4356

IS - 5

ER -