人疟原虫预防药（氯胍）的药代动力学及活化：药物代谢变异性的影响
The pharmacokinetics and activation of proguanil in man: consequences of variability in drug metabolism.
作者信息
Helsby N A, Ward S A, Edwards G, Howells R E, Breckenridge A M
机构信息
Department of Parasitology, Liverpool School of Tropical Medicine.
出版信息
Br J Clin Pharmacol. 1990 Oct;30(4):593-8. doi: 10.1111/j.1365-2125.1990.tb03818.x.
Abstract
- Based on the ratio of drug to active metabolite excreted in urine approximately 3% of a healthy Caucasian population showed a reduced ability to convert proguanil to cycloguanil. 2. Pharmacokinetic analysis showed that this observation resulted from a reduced oral clearance of proguanil in these individuals (245, 534 and 552 ml min-1) compared with the rest of the population (858 +/- 482 ml min-1). 3. Peak plasma concentrations of active metabolite were significantly lower in these subjects (54.2, 26.8 and 51.7 ng ml-1) compared with the rest of the population (141 +/- 45.2 ng ml-1). 4. The observed variability may result from the polymorphic metabolism of proguanil in man.
摘要
- 根据尿中排泄的药物与活性代谢物的比例，约3%的健康白种人群将氯胍转化为环氯胍的能力降低。2. 药代动力学分析表明，这一观察结果是由于这些个体中氯胍的口服清除率降低（分别为245、534和552毫升/分钟），与其他人群（858±482毫升/分钟）相比。3. 这些受试者中活性代谢物的血浆峰值浓度显著低于其他人群（分别为54.2、26.8和51.7纳克/毫升），其他人群为（141±45.2纳克/毫升）。4. 观察到的变异性可能是由于人体中氯胍的多态性代谢所致。
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本文引用的文献
1
Mephenytoin hydroxylation deficiency in Caucasians: frequency of a new oxidative drug metabolism polymorphism.
Clin Pharmacol Ther. 1984 Dec;36(6):773-80. doi: 10.1038/clpt.1984.256.
2
Pharmacogenetics of mephenytoin: a new drug hydroxylation polymorphism in man.
Eur J Clin Pharmacol. 1984;26(6):753-9. doi: 10.1007/BF00541938.
3
Determination of proguanil and its metabolites cycloguanil and 4-chlorophenylbiguanide in plasma, whole blood and urine by high-performance liquid chromatography.
J Chromatogr. 1987 May 15;416(2):394-9. doi: 10.1016/0378-4347(87)80526-1.
4
Single dose pharmacokinetics of proguanil and its metabolites in healthy subjects.
Br J Clin Pharmacol. 1987 Dec;24(6):775-80. doi: 10.1111/j.1365-2125.1987.tb03245.x.
5
A preliminary pharmacokinetic study of the antimalarial drugs, proguanil and chlorproguanil.
J Pharm Pharmacol. 1987 Apr;39(4):261-5. doi: 10.1111/j.2042-7158.1987.tb06263.x.
6
Characterization and inhibition of mephenytoin 4-hydroxylase activity in human liver microsomes.
J Pharmacol Exp Ther. 1987 Jan;240(1):216-22.
7
Inter-subject variability in the metabolism of proguanil to the active metabolite cycloguanil in man.
Br J Clin Pharmacol. 1989 Jun;27(6):781-7. doi: 10.1111/j.1365-2125.1989.tb03440.x.
8
Defective N-oxidation of sparteine in man: a new pharmacogenetic defect.
Eur J Clin Pharmacol. 1979 Sep;16(3):183-7. doi: 10.1007/BF00562059.
9
Polymorphic hydroxylation of Debrisoquine in man.
Lancet. 1977 Sep 17;2(8038):584-6. doi: 10.1016/s0140-6736(77)91430-1.
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