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1
Effect of phenobarbital on plasma levels of cyclophosphamide and its metabolites in the mouse.苯巴比妥对小鼠血浆中环磷酰胺及其代谢产物水平的影响。
Br J Cancer. 1978 Aug;38(2):316-24. doi: 10.1038/bjc.1978.204.
2
Blood levels of alkylating metabolites of cyclophosphamide in the mouse after iv or oral administration.静脉注射或口服给药后小鼠体内环磷酰胺烷基化代谢产物的血药浓度。
Cancer Treat Rep. 1984 May;68(5):765-70.
3
The effect of phenobarbital on cyclophosphamide antitumor activity.苯巴比妥对环磷酰胺抗肿瘤活性的影响。
Cancer Res. 1976 Aug;36(8):2785-9.
4
Phosphoramide mustard is responsible for the ovarian toxicity of cyclophosphamide.磷酰胺氮芥是环磷酰胺卵巢毒性的原因。
Toxicol Appl Pharmacol. 1991 Mar 1;107(3):472-81. doi: 10.1016/0041-008x(91)90310-b.
5
Isophosphoramide mustard, a metabolite of ifosfamide with activity against murine tumours comparable to cyclophosphamide.异环磷酰胺氮芥，异环磷酰胺的一种代谢产物，其对鼠肿瘤的活性与环磷酰胺相当。
Br J Cancer. 1983 Jan;47(1):15-26. doi: 10.1038/bjc.1983.2.
6
Effect of phenobarbital on cyclophosphamide cytotoxic activity and pharmacokinetics in mice.苯巴比妥对小鼠环磷酰胺细胞毒性活性及药代动力学的影响。
Tumori. 1977 Mar-Apr;63(2):137-46. doi: 10.1177/030089167706300203.
7
Plasma concentrations of 4-hydroxycyclophosphamide and phosphoramide mustard in patients repeatedly given high doses of cyclophosphamide in preparation for bone marrow transplantation.在为骨髓移植做准备而反复给予高剂量环磷酰胺的患者中，4-羟基环磷酰胺和磷酰胺氮芥的血浆浓度。
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Brain and plasma pharmacokinetics and anticancer activities of cyclophosphamide and phosphoramide mustard in the rat.环磷酰胺和磷酰胺芥在大鼠体内的脑和血浆药代动力学及抗癌活性
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Half-life of oxazaphosphorines in biological fluids.生物体液中氮杂磷三环类化合物的半衰期。
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Investigation on cyclophosphamide treatment during the preimplantation period. II. In vitro studies on the effects of cyclophosphamide and its metabolites 4-OH-cyclophosphamide, phosphoramide mustard, and acrolein on blastulation of four-cell and eight-cell mouse embryos and on their subsequent development during implantation.着床前期环磷酰胺治疗的研究。II. 环磷酰胺及其代谢产物4-羟基环磷酰胺、磷酰胺氮芥和丙烯醛对四细胞和八细胞小鼠胚胎囊胚形成及其着床期后续发育影响的体外研究
Teratology. 1981 Feb;23(1):7-13. doi: 10.1002/tera.1420230104.

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1
Successful hematopoietic stem cell transplantation following a cyclophosphamide-containing preparative regimen with concomitant phenobarbital administration.在含环磷酰胺的预处理方案并同时给予苯巴比妥的情况下成功进行造血干细胞移植。
Case Rep Transplant. 2012;2012:721857. doi: 10.1155/2012/721857. Epub 2012 Oct 11.
2
Drug interactions in childhood cancer.儿童癌症中的药物相互作用。
Lancet Oncol. 2011 Jan;12(1):92-9. doi: 10.1016/S1470-2045(10)70105-4. Epub 2010 Sep 22.
3
The pharmacokinetics of cyclophosphamide, phosphoramide mustard and nor-nitrogen mustard studied by gas chromatography in patients receiving cyclophosphamide therapy.采用气相色谱法研究接受环磷酰胺治疗的患者中环磷酰胺、磷酰胺氮芥和去甲氮芥的药代动力学。
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Br J Cancer. 1982 Jan;45(1):35-43. doi: 10.1038/bjc.1982.5.
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Isophosphoramide mustard, a metabolite of ifosfamide with activity against murine tumours comparable to cyclophosphamide.异环磷酰胺氮芥，异环磷酰胺的一种代谢产物，其对鼠肿瘤的活性与环磷酰胺相当。
Br J Cancer. 1983 Jan;47(1):15-26. doi: 10.1038/bjc.1983.2.
7
Evidence for chromosomal replicons as units of sister chromatid exchanges.染色体复制子作为姐妹染色单体交换单位的证据。
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8
The effect of cimetidine on cyclophosphamide metabolism in rabbits.西咪替丁对兔体内环磷酰胺代谢的影响。
Cancer Chemother Pharmacol. 1990;27(2):125-30. doi: 10.1007/BF00689096.
9
Clinical pharmacokinetics of cyclophosphamide.环磷酰胺的临床药代动力学
Clin Pharmacokinet. 1979 Sep-Oct;4(5):380-94. doi: 10.2165/00003088-197904050-00004.

本文引用的文献

1
REDUCTION OF PSEUDOMONAS AERUGINOSA AND COLIFORM BACTERIA IN MOUSE DRINKING WATER FOLLOWING TREATMENT WITH HYDROCHLORIC ACID OR CHLORINE.用盐酸或氯处理后小鼠饮用水中铜绿假单胞菌和大肠菌群细菌数量的减少
Lab Anim Care. 1963 Oct;13:737-44.
2
Effect of microsomal enzyme modifiers on toxicity and therapeutic activity of cyclophosphamide in mice.微粒体酶修饰剂对环磷酰胺在小鼠体内毒性及治疗活性的影响。
Arch Int Pharmacodyn Ther. 1969 Aug;180(2):391-401.
3
Pharmacodynamics of chemotherapeutic effects: dose-time-response relationships for phase-nonspecific agents.化疗效果的药效学：非特异性时相药物的剂量-时间-反应关系
J Pharm Sci. 1971 Jun;60(6):892-5. doi: 10.1002/jps.2600600618.
4
Urinary metabolites of the antitumor agent cyclophosphamide.抗肿瘤药物环磷酰胺的尿液代谢产物。
Mol Pharmacol. 1971 Sep;7(5):519-29.
5
Therapeutic efficacy of cyclophosphamide as a function of its metabolism.环磷酰胺的治疗效果与其代谢的关系。
Cancer Res. 1972 Mar;32(3):535-42.
6
Metabolism of cyclophosphamide by sheep.绵羊对环磷酰胺的代谢
J Agric Food Chem. 1972 Mar-Apr;20(2):384-8. doi: 10.1021/jf60180a054.
7
The effect of phenobarbital or 2-diethylaminoethyl-2,2-diphenylvalerate on the activation of cyclophosphamide in vivo.苯巴比妥或2-二乙氨基乙基-2,2-二苯基戊酸酯对环磷酰胺体内活化的影响。
J Pharmacol Exp Ther. 1972 Feb;180(2):475-83.
8
Some studies of the active intermediates formed in the microsomal metabolism of cyclophosphamide and isophosphamide.一些关于环磷酰胺和异环磷酰胺微粒体代谢过程中形成的活性中间体的研究。
Biochem Pharmacol. 1974 Jan 1;23(1):115-29. doi: 10.1016/0006-2952(74)90318-9.
9
A biologically active metabolite of cyclophosphamide.环磷酰胺的一种生物活性代谢物。
Cancer Res. 1973 Apr;33(4):915-8.
10
Evidence for an aldehyde possessing alkylating activity as the primary metabolite of cyclophosphamide.有证据表明，一种具有烷基化活性的醛是环磷酰胺的主要代谢产物。
Cancer Res. 1973 Apr;33(4):651-8.

苯巴比妥对小鼠血浆中环磷酰胺及其代谢产物水平的影响。

Effect of phenobarbital on plasma levels of cyclophosphamide and its metabolites in the mouse.

作者信息

Alberts D S, Peng Y M, Chen H S, Struck R F

出版信息

Br J Cancer. 1978 Aug;38(2):316-24. doi: 10.1038/bjc.1978.204.

DOI:10.1038/bjc.1978.204
PMID:698048
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2009716/
Abstract

We have studied the quantitative pharmacokinetic differences of individual metabolites and unchanged cyclophosphamide (CPA) in control and phenobarbital-treated animals, using radiolabelled CPA together with thin-layer chromatography. On Day 0, one group was started on phenobarbital drinking water and one group stayed on regular acid water. P388 leukaemia, (10(6) cells i.p.) was administered to all mice on Day 8, and 2 days later both groups of mice were given i.p. CPA (200 mg/kg) with 14C-CPA (0.2 muCi per mouse). At 5--60 min after CPA administration, groups of 10 mice were killed and their blood collected for assay of parent compound and metabolites in plasma. Phenobarbital pretreatment reduced CPA and phosphoramide mustard CXT (concentration x time) by 66+% and 27+%, respectively. Assuming that phosphoramide mustard is both the ultimate cytotoxic form of CPA and the blood-transport form, the reduction of CPA by phenobarbital would predict a decreased therapeutic effect. The assay methods in this study will be used in the future to determine the importance of this potential drug interaction in man.

摘要

我们使用放射性标记的环磷酰胺（CPA）结合薄层色谱法，研究了对照动物和苯巴比妥处理动物中各代谢物及未变化的CPA的定量药代动力学差异。在第0天，一组开始饮用含苯巴比妥的水，另一组继续饮用常规酸性水。在第8天给所有小鼠腹腔注射P388白血病细胞（10⁶个细胞），2天后两组小鼠腹腔注射CPA（200mg/kg）及¹⁴C-CPA（每只小鼠0.2μCi）。在注射CPA后5 - 60分钟，每组取10只小鼠处死，收集血液用于检测血浆中母体化合物和代谢物。苯巴比妥预处理分别使CPA和磷酰胺氮芥的浓度 - 时间曲线下面积（CXT）降低了66%以上和27%以上。假设磷酰胺氮芥既是CPA的最终细胞毒性形式又是血液转运形式，那么苯巴比妥使CPA减少可能预示着治疗效果降低。本研究中的检测方法未来将用于确定这种潜在药物相互作用在人体中的重要性。