Sakurai Y, Nakahara T, Takahashi R
Psychopharmacologia. 1975 Oct 31;44(2):195-203. doi: 10.1007/BF00421010.
A dose of 50 mg of chlorpromazine (CPZ) was given to 6 untreated schizophrenic patients and 8 healthy volunteers at 7:00 a.m. before breakfast. Blood samples were taken 3, 6, 9 and 24 hrs after for the analyses of CPZ and its metabolites by gas chromatographic techniques. In the cases of schizophrenic patients, the CPZ treatment was continued. Serum drug levels were monitored and clinical response assessed. The drug levels in serum of another group of patients already under long term treatment were also determined. Although wide inter-patients variations in serum drug levels after a single dose administration were observed, the CPZ level in the patients decreased faster than in the normal subjects. Patients showing high levels of the metabolites such as demethylated CPZ and CPZ sulfoxide after a single dose of CPZ tended to achieve poorer clinical improvement in CPZ therapy, agreeing with the results that poor responders to long term CPZ treatment revealed relatively high levels of the metabolites of CPZ compared with CPZ level. The results indicate that the study of a single dose administration prior to initiating treatment with CPZ can be used to determine how an individual patient would respond to CPZ therapy and be a valuable tool in the rational pharmacotherapy of schizophrenic patients.
早餐前的上午7点,给6名未经治疗的精神分裂症患者和8名健康志愿者服用50毫克氯丙嗪(CPZ)。服药后3、6、9和24小时采集血样,采用气相色谱技术分析CPZ及其代谢产物。对于精神分裂症患者,继续进行CPZ治疗。监测血清药物水平并评估临床反应。还测定了另一组长期接受治疗患者的血清药物水平。尽管单次给药后患者血清药物水平存在很大差异,但患者体内CPZ水平下降速度比正常受试者更快。单次服用CPZ后,代谢产物如去甲基氯丙嗪和氯丙嗪亚砜水平较高的患者,在CPZ治疗中临床改善往往较差,这与长期接受CPZ治疗反应不佳的患者相比,其CPZ代谢产物水平相对较高的结果一致。结果表明,在开始使用CPZ治疗前进行单次给药研究,可用于确定个体患者对CPZ治疗的反应,是精神分裂症患者合理药物治疗的有价值工具。