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精神分裂症患者对氯丙嗪治疗反应的预测。

Prediction of response to chlorpromazine treatment in schizophrenics.

作者信息

Sakurai Y, Nakahara T, Takahashi R

出版信息

Psychopharmacologia. 1975 Oct 31;44(2):195-203. doi: 10.1007/BF00421010.

DOI:10.1007/BF00421010
PMID:1105634
Abstract

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.

摘要

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。

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Prediction of response to chlorpromazine treatment in schizophrenics.精神分裂症患者对氯丙嗪治疗反应的预测。
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引用本文的文献

1
Predictive indices for chlorpromazine therapy in schizophrenics.精神分裂症患者氯丙嗪治疗的预测指标。
Br J Clin Pharmacol. 1982 Aug;14(2):273-7. doi: 10.1111/j.1365-2125.1982.tb01973.x.
2
Fluphenazine pharmacokinetics and therapeutic response.氟奋乃静的药代动力学与治疗反应。
Psychopharmacology (Berl). 1981;73(3):205-10. doi: 10.1007/BF00422403.
3
Concentrations of chlorpromazine and two of its active metabolites in plasma and cerebrospinal fluid of psychotic patients treated with fixed drug doses.接受固定药物剂量治疗的精神病患者血浆和脑脊液中氯丙嗪及其两种活性代谢物的浓度。

本文引用的文献

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A quantitative study of chlorpromazine and its sulfoxides in the urine of psychotic patients.精神病患者尿液中氯丙嗪及其亚砜的定量研究。
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Isolation and characterization of glucuronic acid conjugates of chlorpromazine in human urine.人尿中氯丙嗪葡萄糖醛酸结合物的分离与鉴定
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Dopamine, serotonin and alpha-adrenergic receptor blocking activities in serum and their relationships to prolactin level in schizophrenic patients receiving long-term chlorpromazine treatment.长期接受氯丙嗪治疗的精神分裂症患者血清中的多巴胺、5-羟色胺及α-肾上腺素能受体阻断活性及其与催乳素水平的关系。
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Formation of chlorpromazine sulphoxide and monodesmethylchlorpromazine by microsomes of small intestine.小肠微粒体形成氯丙嗪亚砜和单去甲基氯丙嗪。
Naunyn Schmiedebergs Arch Pharmacol. 1977 Mar;297(2):195-200. doi: 10.1007/BF00499931.
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Chlorpromazine metabolism. IX. Pharmacokinetics of chlorpromazine following oral administration in man.氯丙嗪的代谢。IX. 氯丙嗪在人体口服后的药代动力学。
J Pharmacokinet Biopharm. 1978 Jun;6(3):187-96. doi: 10.1007/BF01312261.
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Plasma level monitoring of antipsychotic drugs.抗精神病药物的血药浓度监测
Clin Pharmacokinet. 1978 Jan-Feb;3(1):14-38. doi: 10.2165/00003088-197803010-00002.
Arch Neurol. 1964 Dec;11:642-8. doi: 10.1001/archneur.1964.00460240074010.
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Urinary thorazine metabolites in psychotic patients.精神病患者尿液中的氯丙嗪代谢物。
Arch Gen Psychiatry. 1963 Mar;8:301-7. doi: 10.1001/archpsyc.1963.01720090089011.
5
Metabolism of chlorpromazine. III. Isolation and identification of chlorpromazine-N-oxide.氯丙嗪的代谢。III. 氯丙嗪 -N-氧化物的分离与鉴定。
Proc Soc Exp Biol Med. 1962 Mar;109:548-52. doi: 10.3181/00379727-109-27264.
6
Metabolism of chlorpromazine: organic-extractable fraction from human urine.氯丙嗪的代谢:来自人类尿液的可有机萃取部分。
Proc Soc Exp Biol Med. 1960 May;104:99-103. doi: 10.3181/00379727-104-25741.
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Fate, distribution and excretion of S35 promazine.S35丙嗪的命运、分布及排泄
J Pharmacol Exp Ther. 1959 Apr;125(4):283-6.
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Identification and pharmacological properties of a major metabolite of chlorpromazine.氯丙嗪主要代谢物的鉴定及其药理特性
Nature. 1955 Dec 10;176(4493):1122-3. doi: 10.1038/1761122a0.
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The metabolism of chlorpromazine by liver microsomal enzyme systems.氯丙嗪在肝脏微粒体酶系统中的代谢。
J Pharmacol Exp Ther. 1967 Aug;157(2):446-58.
10
Determination of nanogram quantities of chlorpromazine and some of its metabolites in plasma using gas-liquid chromatography with an electron capture detector.使用带有电子捕获检测器的气液色谱法测定血浆中纳克量的氯丙嗪及其一些代谢物。
Anal Chem. 1968 Jul;40(8):1251-5. doi: 10.1021/ac60264a031.