Bergemann N, Frick A, Parzer P, Kopitz J
Department of Psychiatry, University of Heidelberg, Germany.
Pharmacopsychiatry. 2004 Mar;37(2):63-8. doi: 10.1055/s-2004-815527.
Olanzapine, a thienobenzodiazepine, is one of the relatively new atypical antipsychotic drugs. The lowest threshold of effective olanzapine plasma levels in inpatient treatment is assumed to be 9 ng/ml. Very little is known about the plasma concentration in patients at various oral doses of olanzapine or about the clinically relevant interactions with co-medications.
In 71 schizophrenic patients (age 32.6 +/- 12.1, range 18-63 years; 31 women, 40 men), plasma olanzapine levels were assessed in 377 tests by high-performance liquid chromatography (HPLC) with electrochemical detection. Fifty-six of these plasma levels were assessed while patients were receiving olanzapine as monotherapy; otherwise, the plasma levels were assessed with the patients receiving various co-medications.
The mean daily oral dose of olanzapine was 17.5 mg (SD = 7.0, range 5-40 mg), and the mean olanzapine plasma concentration was 54.2 ng/ml (SD 37.8 ng/ml, range 1.2-208 ng/ml). The plasma concentration of olanzapine increased linearly with the daily oral dose (r = 0.64, p < 0.001). A multiple variance analysis considering age and sex as covariables showed a significant difference in the dose-corrected plasma levels of olanzapine among 40 smokers and 31 non-smokers; age and sex did not affect the dose-corrected plasma levels. However, women received a significantly lower daily dose of olanzapine under routine clinical study conditions. No differences could be detected among the dose-corrected plasma concentration of those patients who were taken off olanzapine because they did not respond (n = 14) or because of side effects (n = 5) and those who were discharged while still on olanzapine. Under the co-medication with fluvoxamine, significantly higher dose-corrected olanzapine plasma concentrations were found than with olanzapine monotherapy, whereas significantly lower dose-corrected olanzapine plasma concentrations were detected under lithium and trimipramine co-medication. Under co-medication with amitriptyline, benperidol, carbamazepine, flupentixol, and lorazepam, the dose-corrected olanzapine plasma concentrations were no different than the plasma levels under olanzapine monotherapy.
The relevance of therapeutic drug monitoring is emphasized with respect to the data presented and to the literature. Future studies should examine, in particular, the effects of a wider range of co-medications in a larger patient sample.
奥氮平是一种噻吩并苯二氮䓬类药物，是相对较新的非典型抗精神病药物之一。住院治疗中奥氮平有效血浆水平的最低阈值假定为9纳克/毫升。对于不同口服剂量奥氮平患者的血浆浓度，或与联合用药的临床相关相互作用，人们了解甚少。
在71例精神分裂症患者（年龄32.6±12.1岁，范围18 - 63岁；女性31例，男性40例）中，采用高效液相色谱法（HPLC）和电化学检测法，在377次检测中评估了血浆奥氮平水平。其中56次血浆水平评估是在患者接受奥氮平单药治疗时进行的；否则，血浆水平评估是在患者接受各种联合用药时进行的。
奥氮平的平均每日口服剂量为17.5毫克（标准差 = 7.0，范围5 - 40毫克），奥氮平平均血浆浓度为54.2纳克/毫升（标准差37.8纳克/毫升，范围1.2 - 208纳克/毫升）。奥氮平血浆浓度随每日口服剂量呈线性增加（r = 0.64，p < 0.001）。将年龄和性别作为协变量的多变量分析显示，40名吸烟者和31名非吸烟者之间奥氮平剂量校正后的血浆水平存在显著差异；年龄和性别不影响剂量校正后的血浆水平。然而，在常规临床研究条件下，女性接受的奥氮平每日剂量显著较低。因无反应（n = 14）或因副作用（n = 5）停用奥氮平的患者与仍在服用奥氮平出院的患者之间，剂量校正后的血浆浓度未发现差异。与氟伏沙明联合用药时，发现剂量校正后的奥氮平血浆浓度显著高于奥氮平单药治疗时，而与锂盐和曲米帕明联合用药时，检测到剂量校正后的奥氮平血浆浓度显著较低。与阿米替林、苯哌利多、卡马西平、氟哌噻吨和劳拉西泮联合用药时，剂量校正后的奥氮平血浆浓度与奥氮平单药治疗时的血浆水平无差异。
鉴于所呈现的数据和文献，强调了治疗药物监测的相关性。未来的研究尤其应在更大的患者样本中研究更广泛的联合用药的影响。
