Spina E, Avenoso A, Facciolà G, Fabrazzo M, Monteleone P, Maj M, Perucca E, Caputi A P
Institute of Pharmacology, University of Messina, Italy.
Int Clin Psychopharmacol. 1998 May;13(3):141-5. doi: 10.1097/00004850-199805000-00009.
The effect of fluoxetine on the plasma concentrations of clozapine and its major metabolites was studied in 10 schizophrenic patients with residual negative symptoms. Patients stabilized on clozapine therapy (200-450 mg/day) received additional fluoxetine (20 mg/day) for eight consecutive weeks. During fluoxetine administration, mean plasma concentrations of clozapine, norclozapine and clozapine N-oxide increased significantly by 58%, 36% and 38%, respectively. There was no difference in negative symptomatology, as measured by the Scale for Assessment of Negative Symptoms, and the drug combination was generally well tolerated. The concomitant elevation in plasma levels of clozapine and its major metabolites suggests that fluoxetine inhibits the metabolism of clozapine by affecting pathways other than N-demethylation and N-oxidation. Close monitoring of clinical response and, possibly, plasma clozapine levels is recommended whenever fluoxetine is given to patients stabilized on clozapine therapy.
在10例有残留阴性症状的精神分裂症患者中，研究了氟西汀对氯氮平及其主要代谢产物血浆浓度的影响。接受氯氮平治疗（200 - 450毫克/天）病情稳定的患者连续八周额外服用氟西汀（20毫克/天）。在服用氟西汀期间，氯氮平、去甲氯氮平和氯氮平氮氧化物的平均血浆浓度分别显著升高了58%、36%和38%。通过阴性症状评定量表测量，阴性症状学方面没有差异，并且该药物组合总体耐受性良好。氯氮平及其主要代谢产物血浆水平的同时升高表明，氟西汀通过影响除N - 去甲基化和N - 氧化之外的途径抑制氯氮平的代谢。当给服用氯氮平治疗病情稳定的患者使用氟西汀时，建议密切监测临床反应，并可能监测血浆氯氮平水平。
