Original ContributionsHigh Correlation Between Serum and Cerebrospinal Fluid Olanzapine Concentrations in Patients With Schizophrenia or Schizoaffective Disorder Medicating With Oral Olanzapine as the Only Antipsychotic DrugSkogh, Elisabeth MD*; Sjödin, Ingemar MD, PhD*; Josefsson, Martin PhD†‡; Dahl, Marja-Liisa MD, PhD§∥Author Information From the *Department of Clinical and Experimental Medicine, Psychiatry Section, Faculty of Health Science, Linköping University; †The National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology; and ‡Department of Physics, Chemistry and Biology, Linköping University, Linköping; §Department of Medical Sciences, Clinical Pharmacology, University Hospital, Uppsala; and ∥Department of Clinical Pharmacology, Karolinska University Hospital Huddinge, Stockholm, Sweden. Received March 1, 2010; accepted after revision November 2, 2010. Reprints: Elisabeth Skogh, MD, Department of Clinical and Experimental Medicine, Division of Psychiatry, Faculty of Health Sciences, University Hospital, SE-58185 Linköping, Sweden (e-mail: [email protected]). This study was financially supported by the Swedish Psychiatry Foundation and The Swedish Research Council (2008-2578). Journal of Clinical Psychopharmacology: February 2011 - Volume 31 - Issue 1 - p 4-9 doi: 10.1097/JCP.0b013e318204d9e2 Buy Metrics Abstract The primary aim of the present study was to investigate the relationship between steady state serum and cerebrospinal fluid (CSF) concentrations of olanzapine (OLA) and its metabolite 4′-N-desmethylolanzapine (DMO) in patients with schizophrenia or schizoaffective disorder treated with oral OLA as the only antipsychotic drug. The influence of smoking, gender, age, as well as polymorphisms in cytochrome P450 CYP2D6, CYP1A2, and ABCB1 genes on the serum and CSF drug levels was also analyzed. Thirty-seven white outpatients (10 smokers and 27 nonsmokers) were included. From 29 of them, CSF was collected successfully. A strong correlation (Spearman rank correlation [rs] = 0.93; P < 0.05) was found between serum and CSF concentrations of OLA and a somewhat weaker correlation (rs = 0.5; P < 0.05) between those of DMO. The CSF concentrations of OLA and DMO were on average 12% and 16% of those in serum. Extensive metabolizers of CYP2D6 had higher (P < 0.05) daily doses than poor metabolizers when the influence of smoking was taken into account. Smokers had lower (P < 0.01) concentration-to-dose ratios of OLA in serum (mean, 2.23 ng/mL per mg vs 3.32 ng/mL per mg) and CSF (0.27 ng/mL per mg vs 0.41 ng/mL per mg) than nonsmokers. The concentration-to-dose ratio for serum DMO decreased with increasing age (rs = −0.41; P < 0.05). Carriers of ABCB1 1236T/2677T/3435T haplotype had higher serum (mean, 37.7 ng/mL vs 22.5 ng/mL; P = 0.035) and CSF (4.7 ng/mL vs 2.6 ng/mL; P = 0.018) OLA concentrations than patients without this haplotype. The present study shows a strong correlation between serum and CSF concentrations of OLA, indicating that concentrations of OLA in serum reflect those in CSF. © 2011 by Lippincott Williams & Wilkins.