Baldessarini R J, Centorrino F, Flood J G, Volpicelli S A, Huston-Lyons D, Cohen B M
Consolidated Department of Psychiatry and Neuroscience Program, Harvard Medical School, McLean Hospital, Belmont, MA 02178.
Neuropsychopharmacology. 1993 Sep;9(2):117-24. doi: 10.1038/npp.1993.50.
Clozapine (CLZ) and its metabolites norclozapine (NOR) and clozapine-N-oxide (NOX) were assayed in rat serum and brain tissue after intraperitoneal injection of CLZ. Clozapine levels rose with dose, averaging 28 ng/ml (87 nmol/L) serum per milligram/kilogram dose. Brain- and serum-CLZ levels correlated closely, averaging 24-fold higher in brain. Norclozapine and NOX averaged approximately 58% and 13% of CLZ in serum, respectively, whereas in brain, NOR was detected only at doses greater than or equal to 10 mg/kg (approximately 5.6% of CLZ) and NOX was undetectable. Levels peaked within 30 minutes, and elimination of CLZ from brain and CLZ or NOR from blood was very rapid (half-life = 1.5 to 1.6 hours). A week of daily dosing with CLZ led to no accumulation of drug in brain; a week of fluoxetine pretreatment increased analyte concentrations (serum, 86%; brain, 61%), but valproate had little effect.
腹腔注射氯氮平后，对大鼠血清和脑组织中的氯氮平（CLZ）及其代谢产物去甲氯氮平（NOR）和氯氮平 - N - 氧化物（NOX）进行了测定。氯氮平水平随剂量升高，每毫克/千克剂量的血清平均浓度为28纳克/毫升（87纳摩尔/升）。脑和血清中的氯氮平水平密切相关，脑中的平均浓度比血清中高约24倍。血清中去甲氯氮平和NOX的平均含量分别约为氯氮平的58%和13%，而在脑中，仅在剂量大于或等于10毫克/千克（约为氯氮平的5.6%）时才检测到去甲氯氮平，未检测到NOX。浓度在30分钟内达到峰值，氯氮平从脑中消除以及氯氮平或去甲氯氮平从血液中消除都非常迅速（半衰期 = 1.5至1.6小时）。连续一周每日给予氯氮平不会导致药物在脑中蓄积；一周的氟西汀预处理会增加分析物浓度（血清中增加86%，脑中增加61%），但丙戊酸盐几乎没有影响。
