氯氮平治疗精神分裂症的血药浓度与临床疗效及不良反应的关系

目的探讨氯氮平治疗精神分裂症的血药浓度与临床疗效及不良反应的关系。方法采用高效液相反相色谱法进行氯氮平血药浓度监测,并对患者的服药剂量、血药浓度、临床疗效及不良反应进行统计分析。结果不同剂量血药浓度差异有显著性;低浓度与中、高浓度氯氮平血药浓度临床疗效差异有显著性(P<0.05);不同去甲氯氮平血药浓度临床疗效差异有显著性(P<0.05);不同血药浓度不良反应差异无显著性(P>0.05)。结论氯氮平的血药浓度监测对指导个体化合理用药具有临床意义。     

同等剂量氯氮平血药浓度与临床疗效的关系

目的 :探讨同等剂量氯氮平血药浓度与临床疗效的关系。方法 :以固定剂量氯氮平 ( 3 0 0mg·d-1)治疗 61例精神分裂症患者。疗效用简明精神病评定量表 (BPRS)进行评定 ,并测定治疗wk 2及wk 3的血药浓度。结果 :氯氮平及去甲氯氮平血药浓度与临床疗效有明显关系 ,尤以去甲氯氮平血药浓度与临床疗效关系更为密切。结论 :氯氮平及去甲氯氮平血药浓度的监测有助于指导临床个体化合理用药     

Clozapine-induced salivation: interaction with N-desmethylclozapine and amisulpride in an experimental rat model

Many drugs (e.g. amisulpride) have been used to treat troublesome clozapine-induced salivation; however, varying success has been achieved in this respect, probably because, until recently, the salivatory action of clozapine has been largely unexplained. In the rat, clozapine and its main metabolite, N-desmethylclozapine, were found to exert mixed secretory actions: excitatory, through muscarinic acetylcholine M1-receptors giving rise to a long-lasting, low-level flow of saliva; and inhibitory, through muscarinic M3-receptors and α(1) -adrenoceptors reducing the parasympathetically and sympathetically nerve-evoked flow of saliva. The aim of the present study was to define the interactions between clozapine and N-desmethylclozapine, and clozapine and amisulpride, with respect to the excitatory response. Submandibular glands, sensitized by chronic parasympathetic preganglionic denervation, were studied in pentobarbitone-anaesthetized rats. To prevent clozapine from being metabolized to N-desmethylclozapine by hepatic enzymes, the liver was, under terminal anaesthesia, excluded from the circulation. The weak receptor-stimulating clozapine prevented the strong receptor-stimulating N-desmethylclozapine, at specific ratios in humans and in rats, from exerting its full agonistic action. In conclusion, the contribution of N-desmethylclozapine to the clozapine-induced sialorrhoea was, at most, only partly additive. Furthermore, the present experimental set-up failed to demonstrate any anti-salivatory action of amisulpride on the clozapine-induced flow of saliva.