Olanzapine in serum and cerebrospinal fluid in patients with schizophrenia or schizoaffective disorder
2010 (English)In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 20, no Suppl. 3, S469-S469 p.Article in journal, Meeting abstract (Other academic) Published
Background: The relationship between serum and CSF concentrations of olanzapine (OLA) in humans has to our knowledge not been described earlier. Few studies have investigated how the CYP2D6 and CYP1A2 polymorphisms affect OLA pharmacoki- netics in humans  . Polymorphisms in the ABCB1 gene have been associated with altered pharmacokinetics of certain drugs including risperidone .The aim of the present study was to investigate the relationship between steady state serum and cerebrospinal ﬂuid (CSF) con- centrations of OLA and its metabolite 4t -N-desmethylolanzapine (DMO) and to address the inﬂuence of smoking, gender, age as well as polymorphisms in genes coding for OLA metabolism (CYP2D6, CYP1A2) and transport (ABCB1) in patients with schizophrenia or schizoaffective disorder, treated with oral OLAas the only antipsychotic drug.
Methods: Thirty seven Caucasian outpatients (10 smokers and27 non-smokers), suffering from schizophrenia or schizoaffective disorder according to DSM-IV criteria were included in the study. From 29 out of them, CSF was collected successfully.Fasting blood samples were collected in the morning for analy- ses of OLA and DMO and for genotyping (polymorphisms of CYP2D6, CYP1A2 and ABCB1). Lumbar puncture was per- formed at close connection to blood sampling at the minimum of eight hours in the fasting state. The blood and CSF samples were stored at −70ºC until analysed.A validated accurate and sensitive LC-MS/MS method was used for the analysis of OLA and DMO. Analytes were quantiﬁed by using linear gradient reversed phase chromatography with tandem mass spectrometry detection operating in positive electro-sprayionization mode with multiple reactions monitoring (MRM).
Results: A strong correlation (rs =0.93; p < 0.05) was foundbetween serum and CSF concentrations of OLA and a somewhatweaker (rs =0.5; p < 0.05) between those of DMO. The CSF con- centrations of OLA and DMO were in average 13% and 16% of those in serum. Extensive metabolizers of CYP2D6 were pre- scribed higher (p < 0.05) daily doses than poor metabolizers when the inﬂuence of smoking habits was taken into account. Smokers had lower concentration-to-dose ratios (C/D) of OLA both in serum and CSF than non-smokers (median 7 vs. 10 nmol/L/mg in serum and 0.8 vs. 1.3 nmol/L/mg in CSF; p < 0.01). C/D for serum DMO decreased with increasing age (rs = −0.41; p < 0.05). Carriers of ABCB1 1236T/2677T/3435T haplotype had higher serum (median 112 vs. 80 nmol/L; p < 0.05) and CSF (13.7 vs. 8.1 nmol/L; p < 0.05) OLA concentrations than patients without this haplotype. Patients treated with benzodiazepines and/or zopiclone (n = 8) had higher DMO and DMO/OLA ratio (p < 0.05 for both) in CSF compared to patients not co-medicating with these drugs (n = 21), even when smoking habits were taken into account.
Conclusion: The present study shows a very good correlation between serum and CSF concentrations of OLA, indicating thatconcentrations of OLA in serum reﬂect the situation in CSF.
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Place, publisher, year, edition, pages
Elsevier, 2010. Vol. 20, no Suppl. 3, S469-S469 p.
Engineering and Technology
IdentifiersURN: urn:nbn:se:liu:diva-63947DOI: 10.1016/S0924-977X(10)70690-8ISI: 000283687800577OAI: oai:DiVA.org:liu-63947DiVA: diva2:384774
The 23rd ECNP Congress, Amsterdam, the Netherlands, 28 August–1 September 2010