Steady‐State Plasma Levels of E‐ and Z‐10‐OH‐Nortriptyline in Nortriptyline‐Treated PatientsSignificance of Concurrent Medication and the Sparteine Oxidation Phenotype
作者:
Lars Gram,
Kim BroSsen,
Per Kragh-SoSrensen,
Peder Christensen,
期刊:
Therapeutic Drug Monitoring
(OVID Available online 1989)
卷期:
Volume 11,
issue 5
页码: 508-514
ISSN:0163-4356
年代: 1989
出版商: OVID
关键词: Hydroxylation;Sparteine/debrisoquine;Interaction;Drug oxidation.
数据来源: OVID
摘要:
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 (rs= 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.
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