4-Hydroxycyclophosphamide (BioDeep_00000006562)
Secondary id: BioDeep_00001868936
human metabolite Endogenous blood metabolite Chemicals and Drugs
代谢物信息卡片
Tetrahydro-2-(bis(2-chloroethyl)amino)-2H-1,3,2-oxazaphosphorin-4-ol 2-oxide
化学式: C7H15Cl2N2O3P (276.0197)
中文名称: (R,S)-4-羟基环磷酰胺
谱图信息:
最多检出来源 Homo sapiens(blood) 35.22%
分子结构信息
SMILES: C1COP(=O)(NC1O)N(CCCl)CCCl
InChI: InChI=1S/C7H15Cl2N2O3P/c8-2-4-11(5-3-9)15(13)10-7(12)1-6-14-15/h7,12H,1-6H2,(H,10,13)
描述信息
4-Hydroxycyclophosphamide is a primary activation metabolite of cyclophosphamide and of mafosfamide (an experimental drug) after they partially metabolized by cytochrome P450 (PMID: 12021633). Cyclophosphamide is a chemotherapeutic used to suppress the immune system and to treat several cancers including lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer and small cell lung cancer. After cyclphosphamide is converted to 4-hydroxycyclophosphamide it is then partially tautomerized into aldophosphamide, which easily enters live cells whereupon it is partially detoxified into inactive carboxycyclophosphamide by the enzyme ALDH. 4-Hydroxycyclophosphamide is also an intermediate metabolite in the formation of phosphoramide mustard, the active metabolite, and acrolein, the metabolite responsible for much of the toxicity associated with cyclophosphamides (PMID: 7059981). 4-Hydroxycyclophosphamide is not cytotoxic at physiologic pH, readily diffuses into cells and spontaneously decomposes into the active phosphoramide mustard. In human liver microsomes, 4-Hydroxycyclophosphamide formation correlates with known phenotypic markers of CYP2B6 activity, specifically formation of (S)-2-ethyl-1,5-dimethyl-3,3-diphenyl pyrrolidine and hydroxybupropion. In addition, it is reported that the CYP2B6 genotype is not consistently related to 4-Hydroxycyclophosphamide formation in vitro or in vivo (PMID: 21976622). 4-Hydroxycyclophosphamide is only found in individuals who have consumed the drug cyclophosphamide.
D000970 - Antineoplastic Agents > D018906 - Antineoplastic Agents, Alkylating > D009588 - Nitrogen Mustard Compounds
D000970 - Antineoplastic Agents > D018906 - Antineoplastic Agents, Alkylating > D010752 - Phosphoramide Mustards
同义名列表
7 个代谢物同义名
Tetrahydro-2-(bis(2-chloroethyl)amino)-2H-1,3,2-oxazaphosphorin-4-ol 2-oxide; 2-[bis(2-chloroethyl)amino]-4-hydroxy-1,3,2λ⁵-oxazaphosphinan-2-one; 4-Hydroxycyclophosphamide, (trans)-isomer; 4-Hydroxycyclophosphamide, (cis)-isomer; (R,S)-4-Hydroxy Cyclophosphamide; 4-Hydroxycyclophosphamide; 4-Hydroxycyclophosphamide
数据库引用编号
14 个数据库交叉引用编号
- ChEBI: CHEBI:1864
- KEGG: C07643
- PubChem: 99735
- HMDB: HMDB0013856
- Metlin: METLIN630
- ChEMBL: CHEMBL731
- Wikipedia: 4-Hydroxycyclophosphamide
- CAS: 40277-05-2
- CAS: 61903-30-8
- PMhub: MS000019624
- PubChem: 9845
- NIKKAJI: J65.704B
- RefMet: 4-Hydroxycyclophosphamide
- KNApSAcK: 1864
分类词条
相关代谢途径
Reactome(5)
BioCyc(0)
PlantCyc(0)
代谢反应
63 个相关的代谢反应过程信息。
Reactome(60)
- Metabolism:
3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-24-one-CoA + CoA-SH ⟶ choloyl-CoA + propionyl CoA - Cytochrome P450 - arranged by substrate type:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Metabolism:
3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-24-one-CoA + CoA-SH ⟶ choloyl-CoA + propionyl CoA - Biological oxidations:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Phase I - Functionalization of compounds:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Cytochrome P450 - arranged by substrate type:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Xenobiotics:
H+ + Oxygen + TPNH + aflatoxin B1 ⟶ AFXBO + H2O + TPN - Phase I - Functionalization of compounds:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Biological oxidations:
H+ + Oxygen + TPNH + aflatoxin B1 ⟶ AFXBO + H2O + TPN - Phase I - Functionalization of compounds:
CH3CHO + H2O + NAD ⟶ CH3COO- + H+ + NADH - Cytochrome P450 - arranged by substrate type:
ANDST + H+ + Oxygen + TPNH ⟶ H2O + HCOOH + TPN + estrone - Xenobiotics:
EtOH + H+ + Oxygen + TPNH ⟶ CH3CHO + H2O + TPN - Metabolism:
1-3-oxo-THA-CoA + CoA-SH ⟶ DHA-CoA + propionyl CoA - Biological oxidations:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Xenobiotics:
H+ + Oxygen + TPNH + aflatoxin B1 ⟶ AFXBO + H2O + TPN - Cytochrome P450 - arranged by substrate type:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Xenobiotics:
H+ + Oxygen + TPNH + aflatoxin B1 ⟶ AFXBO + H2O + TPN - Metabolism:
1-3-oxo-THA-CoA + CoA-SH ⟶ DHA-CoA + propionyl CoA - Biological oxidations:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Phase I - Functionalization of compounds:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Cytochrome P450 - arranged by substrate type:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Xenobiotics:
H+ + Oxygen + TPNH + aflatoxin B1 ⟶ AFXBO + H2O + TPN - Metabolism:
ATP + PROP-CoA + carbon dioxide ⟶ ADP + MEMA-CoA + Pi - Biological oxidations:
H+ + Oxygen + TPNH + aflatoxin B1 ⟶ AFXBO + H2O + TPN - Phase I - Functionalization of compounds:
CH3CHO + H2O + NAD ⟶ CH3COO- + H+ + NADH - Cytochrome P450 - arranged by substrate type:
EtOH + H+ + Oxygen + TPNH ⟶ CH3CHO + H2O + TPN - Xenobiotics:
EtOH + H+ + Oxygen + TPNH ⟶ CH3CHO + H2O + TPN - Metabolism:
1-3-oxo-THA-CoA + CoA-SH ⟶ DHA-CoA + propionyl CoA - Biological oxidations:
CH3CHO + H2O + NAD ⟶ CH3COO- + H+ + NADH - Phase I - Functionalization of compounds:
CH3CHO + H2O + NAD ⟶ CH3COO- + H+ + NADH - Cytochrome P450 - arranged by substrate type:
ANDST + H+ + Oxygen + TPNH ⟶ H2O + HCOOH + TPN + estrone - Xenobiotics:
DEXM + H+ + Oxygen + TPNH ⟶ CH2O + DEXT + H2O + TPN - Metabolism:
2MACA-CoA + CoA ⟶ Ac-CoA + PROP-CoA - Biological oxidations:
H+ + Oxygen + TPNH + progesterone ⟶ 11DCORST + H2O + TPN - Phase I - Functionalization of compounds:
H+ + Oxygen + TPNH + progesterone ⟶ 11DCORST + H2O + TPN - Cytochrome P450 - arranged by substrate type:
H+ + Oxygen + TPNH + progesterone ⟶ 11DCORST + H2O + TPN - Xenobiotics:
H+ + Oxygen + TPNH + aflatoxin B1 ⟶ AFXBO + H2O + TPN - Metabolism:
3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-24-one-CoA + CoA-SH ⟶ choloyl-CoA + propionyl CoA - Biological oxidations:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Phase I - Functionalization of compounds:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Cytochrome P450 - arranged by substrate type:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Xenobiotics:
H+ + Oxygen + TPNH + aflatoxin B1 ⟶ AFXBO + H2O + TPN - Metabolism:
1-3-oxo-THA-CoA + CoA-SH ⟶ DHA-CoA + propionyl CoA - Biological oxidations:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Phase I - Functionalization of compounds:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Cytochrome P450 - arranged by substrate type:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Xenobiotics:
H+ + Oxygen + TPNH + aflatoxin B1 ⟶ AFXBO + H2O + TPN - Metabolism:
2MACA-CoA + CoA ⟶ Ac-CoA + PROP-CoA - Biological oxidations:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Phase I - Functionalization of compounds:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Cytochrome P450 - arranged by substrate type:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Xenobiotics:
H+ + Oxygen + TPNH + aflatoxin B1 ⟶ AFXBO + H2O + TPN - Metabolism:
ATP + PROP-CoA + carbon dioxide ⟶ ADP + MEMA-CoA + Pi - Biological oxidations:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Phase I - Functionalization of compounds:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Cytochrome P450 - arranged by substrate type:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Xenobiotics:
CAF + H+ + Oxygen + TPNH ⟶ CH2O + H2O + Paraxanthine + TPN - Metabolism:
1-3-oxo-THA-CoA + CoA-SH ⟶ DHA-CoA + propionyl CoA - Biological oxidations:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN - Phase I - Functionalization of compounds:
11DCORT + H+ + Oxygen + TPNH ⟶ CORT + H2O + TPN
BioCyc(0)
WikiPathways(0)
Plant Reactome(0)
INOH(0)
PlantCyc(0)
COVID-19 Disease Map(0)
PathBank(2)
- Cyclophosphamide Metabolism Pathway:
Aldophosphamide + Glutathione ⟶ 4-Glutathionyl cyclophosphamide + Water - Cyclophosphamide Action Pathway:
Aldophosphamide + Glutathione ⟶ 4-Glutathionyl cyclophosphamide + Water
PharmGKB(1)
- Cyclophosphamide Pathway, Pharmacokinetics:
cyclophosphamide ⟶ 3-dechloroethyl ifosfamide + chloroacetaldehyde
1 个相关的物种来源信息
在这里通过桑基图来展示出与当前的这个代谢物在我们的BioDeep知识库中具有相关联信息的其他代谢物。在这里进行关联的信息来源主要有：
- PubMed: 来源于PubMed文献库中的文献信息，我们通过自然语言数据挖掘得到的在同一篇文献中被同时提及的相关代谢物列表，这个列表按照代谢物同时出现的文献数量降序排序，取前10个代谢物作为相关研究中关联性很高的代谢物集合展示在桑基图中。
- NCBI Taxonomy: 通过文献数据挖掘，得到的代谢物物种来源信息关联。这个关联信息同样按照出现的次数降序排序，取前10个代谢物作为高关联度的代谢物集合展示在桑吉图上。
- Chemical Taxonomy: 在物质分类上处于同一个分类集合中的其他代谢物
- Chemical Reaction: 在化学反应过程中，存在为当前代谢物相关联的生化反应过程中的反应底物或者反应产物的关联代谢物信息。
点击图上的相关代谢物的名称，可以跳转到相关代谢物的信息页面。
文献列表
- Veatriki N Iliopoulou, Georgia Charkoftaki, Jennifer C Cooper, Aristides Dokoumetzidis, Melanie S Joy. Population pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide metabolite in patients with autoimmune glomerulonephritis.
The Journal of pharmacy and pharmacology.
2021 Dec; 73(12):1683-1692. doi:
10.1093/jpp/rgab135. [PMID: 34480477] - Olivia Campagne, Bo Zhong, Sreenath Nair, Tong Lin, Jie Huang, Arzu Onar-Thomas, Giles Robinson, Amar Gajjar, Clinton F Stewart. Exposure-Toxicity Association of Cyclophosphamide and Its Metabolites in Infants and Young Children with Primary Brain Tumors: Implications for Dosing.
Clinical cancer research : an official journal of the American Association for Cancer Research.
2020 04; 26(7):1563-1573. doi:
10.1158/1078-0432.ccr-19-2685. [PMID: 31796512] - O Morgan Hall, Cody J Peer, Courtney D Fitzhugh, William D Figg. A sensitive and rapid ultra high-performance liquid chromatography with tandem mass spectrometric assay for the simultaneous quantitation of cyclophosphamide and the 4-hydroxycyclophosphamide metabolite in human plasma.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.
2018 Jun; 1086(?):56-62. doi:
10.1016/j.jchromb.2018.04.016. [PMID: 29656084] - Katherine A Stroda, Jacqueline D Murphy, Ryan J Hansen, Lisa Brownlee, Elizabeth A Atencio, Daniel L Gustafson, Susan E Lana. Pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide in cats after oral, intravenous, and intraperitoneal administration of cyclophosphamide.
American journal of veterinary research.
2017 Jul; 78(7):862-866. doi:
10.2460/ajvr.78.7.862. [PMID: 28650232] - Wenying Shu, Su Guan, Xiuyan Yang, Liuqin Liang, Jiali Li, Zhuojia Chen, Yu Zhang, Lingyan Chen, Xueding Wang, Min Huang. Genetic markers in CYP2C19 and CYP2B6 for prediction of cyclophosphamide's 4-hydroxylation, efficacy and side effects in Chinese patients with systemic lupus erythematosus.
British journal of clinical pharmacology.
2016 Feb; 81(2):327-40. doi:
10.1111/bcp.12800. [PMID: 26456622] - Francine Attié de Castro, Gabriel dos Santos Scatena, Otávio Pelegrino Rocha, Maria Paula Marques, Quézia Bezerra Cass, Belinda Pinto Simões, Vera Lucia Lanchote. Enantioselective analysis of 4-hydroxycyclophosphamide in human plasma with application to a clinical pharmacokinetic study.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.
2016 Feb; 1011(?):53-61. doi:
10.1016/j.jchromb.2015.12.049. [PMID: 26760223] - Kirsten C G Van Dycke, Romana M Nijman, Paul F K Wackers, Martijs J Jonker, Wendy Rodenburg, Conny T M van Oostrom, Daniela C F Salvatori, Timo M Breit, Harry van Steeg, Mirjam Luijten, Gijsbertus T J van der Horst. A day and night difference in the response of the hepatic transcriptome to cyclophosphamide treatment.
Archives of toxicology.
2015 Feb; 89(2):221-31. doi:
10.1007/s00204-014-1257-z. [PMID: 24819615] - Melanie S Joy, Mary La, Jinzhao Wang, Arlene S Bridges, Yichun Hu, Susan L Hogan, Reginald F Frye, Joyce Blaisdell, Joyce A Goldstein, Mary Anne Dooley, Kim L R Brouwer, Ronald J Falk. Cyclophosphamide and 4-hydroxycyclophosphamide pharmacokinetics in patients with glomerulonephritis secondary to lupus and small vessel vasculitis.
British journal of clinical pharmacology.
2012 Sep; 74(3):445-55. doi:
10.1111/j.1365-2125.2012.04223.x. [PMID: 22380717] - Nasir Ali Afsar, Mike Ufer, Sierk Haenisch, Cornelia Remmler, Ahmed Mateen, Ahmed Usman, Khwaja Zafar Ahmed, Hakimuddin Razi Ahmad, Ingolf Cascorbi. Relationship of drug metabolizing enzyme genotype to plasma levels as well as myelotoxicity of cyclophosphamide in breast cancer patients.
European journal of clinical pharmacology.
2012 Apr; 68(4):389-95. doi:
10.1007/s00228-011-1134-0. [PMID: 22012257] - Brianne S Raccor, Adam J Claessens, Jean C Dinh, Julie R Park, Douglas S Hawkins, Sushma S Thomas, Karen W Makar, Jeannine S McCune, Rheem A Totah. Potential contribution of cytochrome P450 2B6 to hepatic 4-hydroxycyclophosphamide formation in vitro and in vivo.
Drug metabolism and disposition: the biological fate of chemicals.
2012 Jan; 40(1):54-63. doi:
10.1124/dmd.111.039347. [PMID: 21976622] - Jee Young Kim, Kee Duk Park, David P Richman. Treatment of myasthenia gravis based on its immunopathogenesis.
Journal of clinical neurology (Seoul, Korea).
2011 Dec; 7(4):173-83. doi:
10.3988/jcn.2011.7.4.173. [PMID: 22259613] - Wenying Shu, Xueding Wang, Xiuyan Yang, Liuqin Liang, Jiali Li, Zhuojia Chen, Xiao Chen, Jing Jin, Ruiming Li, Lizi Zhao, Min Huang. Simultaneous determination of cyclophosphamide and 4-hydroxycyclophosphamide in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry - application to Chinese systemic lupus erythematosus patients.
Clinical chemistry and laboratory medicine.
2011 Sep; 49(12):2029-37. doi:
10.1515/cclm.2011.710. [PMID: 21902573] - E Warry, R J Hansen, D L Gustafson, S E Lana. Pharmacokinetics of cyclophosphamide after oral and intravenous administration to dogs with lymphoma.
Journal of veterinary internal medicine.
2011 Jul; 25(4):903-8. doi:
10.1111/j.1939-1676.2011.0730.x. [PMID: 21564295] - K Van Calsteren, R Verbesselt, J Beijnen, R Devlieger, L De Catte, D C Chai, R Van Bree, L Heyns, J de Hoon, F Amant. Transplacental transfer of anthracyclines, vinblastine, and 4-hydroxy-cyclophosphamide in a baboon model.
Gynecologic oncology.
2010 Dec; 119(3):594-600. doi:
10.1016/j.ygyno.2010.08.019. [PMID: 20846713] - Jessica Burkhart, Chantal Wälchli, Peter Heusser, Ulrike Weissenstein, Stephan Baumgartner, Anne-Catherine Andres. In vitro investigation into the potential of a mistletoe extract to alleviate adverse effects of cyclophosphamide.
Alternative therapies in health and medicine.
2010 May; 16(3):40-8. doi:
. [PMID: 20486623] - Corine Ekhart, Sjoerd Rodenhuis, Jos H Beijnen, Alwin D R Huitema. Carbamazepine induces bioactivation of cyclophosphamide and thiotepa.
Cancer chemotherapy and pharmacology.
2009 Feb; 63(3):543-7. doi:
10.1007/s00280-008-0758-y. [PMID: 18437385] - Corine Ekhart, Sjoerd Rodenhuis, Jos H Beijnen, Alwin D R Huitema. Pharmacokinetics of cyclophosphamide and thiotepa in a conventional fractionated high-dose regimen compared with a novel simplified unfractionated regimen.
Therapeutic drug monitoring.
2009 Feb; 31(1):95-103. doi:
10.1097/ftd.0b013e318194e484. [PMID: 19155964] - Corine Ekhart, J Martijn Kerst, Sjoerd Rodenhuis, Jos H Beijnen, Alwin D R Huitema. Altered cyclophosphamide and thiotepa pharmacokinetics in a patient with moderate renal insufficiency.
Cancer chemotherapy and pharmacology.
2009 Jan; 63(2):375-9. doi:
10.1007/s00280-008-0757-z. [PMID: 18431571] - Corine Ekhart, Valerie D Doodeman, Sjoerd Rodenhuis, Paul H M Smits, Jos H Beijnen, Alwin D R Huitema. Influence of polymorphisms of drug metabolizing enzymes (CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, GSTA1, GSTP1, ALDH1A1 and ALDH3A1) on the pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide.
Pharmacogenetics and genomics.
2008 Jun; 18(6):515-23. doi:
10.1097/fpc.0b013e3282fc9766. [PMID: 18496131] - William Matsui, Qiuju Wang, James P Barber, Sarah Brennan, B Douglas Smith, Ivan Borrello, Ian McNiece, Lan Lin, Richard F Ambinder, Craig Peacock, D Neil Watkins, Carol Ann Huff, Richard J Jones. Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance.
Cancer research.
2008 Jan; 68(1):190-7. doi:
10.1158/0008-5472.can-07-3096. [PMID: 18172311] - Arlo Upton, Jeannine S McCune, Katharine A Kirby, Wendy Leisenring, George McDonald, Ami Batchelder, Kieren A Marr. Fluconazole coadministration concurrent with cyclophosphamide conditioning may reduce regimen-related toxicity postmyeloablative hematopoietic cell transplantation.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.
2007 Jul; 13(7):760-4. doi:
10.1016/j.bbmt.2007.03.005. [PMID: 17580253] - Corine Ekhart, Abadi Gebretensae, Hilde Rosing, Sjoerd Rodenhuis, Jos H Beijnen, Alwin D R Huitema. Simultaneous quantification of cyclophosphamide and its active metabolite 4-hydroxycyclophosphamide in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-MS/MS).
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.
2007 Jul; 854(1-2):345-9. doi:
10.1016/j.jchromb.2007.04.024. [PMID: 17485255] - Miki Nakajima, Sayaka Komagata, Yuto Fujiki, Yoshihiro Kanada, Hiromichi Ebi, Kuniaki Itoh, Hirofumi Mukai, Tsuyoshi Yokoi, Hironobu Minami. Genetic polymorphisms of CYP2B6 affect the pharmacokinetics/pharmacodynamics of cyclophosphamide in Japanese cancer patients.
Pharmacogenetics and genomics.
2007 Jun; 17(6):431-45. doi:
10.1097/fpc.0b013e328045c4fb. [PMID: 17502835] - Jun Gu, Chong-Sheng Chen, Yuan Wei, Cheng Fang, Fang Xie, Kurunthachalam Kannan, Weizhu Yang, David J Waxman, Xinxin Ding. A mouse model with liver-specific deletion and global suppression of the NADPH-cytochrome P450 reductase gene: characterization and utility for in vivo studies of cyclophosphamide disposition.
The Journal of pharmacology and experimental therapeutics.
2007 Apr; 321(1):9-17. doi:
10.1124/jpet.106.118240. [PMID: 17218484] - Hong Lu, Kenneth K Chan. Pharmacokinetics of N-2-chloroethylaziridine, a volatile cytotoxic metabolite of cyclophosphamide, in the rat.
Cancer chemotherapy and pharmacology.
2006 Oct; 58(4):532-9. doi:
10.1007/s00280-006-0196-7. [PMID: 16470409] - David H Salinger, Jeannine S McCune, Aaron G Ren, Danny D Shen, John T Slattery, Brian Phillips, George B McDonald, Paolo Vicini. Real-time dose adjustment of cyclophosphamide in a preparative regimen for hematopoietic cell transplant: a Bayesian pharmacokinetic approach.
Clinical cancer research : an official journal of the American Association for Cancer Research.
2006 Aug; 12(16):4888-98. doi:
10.1158/1078-0432.ccr-05-2079. [PMID: 16914577] - M E de Jonge, A D R Huitema, J H Beijnen, S Rodenhuis. High exposures to bioactivated cyclophosphamide are related to the occurrence of veno-occlusive disease of the liver following high-dose chemotherapy.
British journal of cancer.
2006 May; 94(9):1226-30. doi:
10.1038/sj.bjc.6603097. [PMID: 16622453] - Thomas F Kalhorn, William N Howald, Scott Cole, Brian Phillips, Joanne Wang, John T Slattery, Jeannine S McCune. Rapid quantitation of cyclophosphamide metabolites in plasma by liquid chromatography-mass spectrometry.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.
2006 May; 835(1-2):105-13. doi:
10.1016/j.jchromb.2006.03.022. [PMID: 16581318] - Hanjing Xie, Laimonas Griskevicius, Lars Ståhle, Zuzana Hassan, Umit Yasar, Anders Rane, Ulrika Broberg, Eva Kimby, Moustapha Hassan. Pharmacogenetics of cyclophosphamide in patients with hematological malignancies.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.
2006 Jan; 27(1):54-61. doi:
10.1016/j.ejps.2005.08.008. [PMID: 16183265] - Milly E de Jonge, Alwin D R Huitema, Selma M van Dam, Sjoerd Rodenhuis, Jos H Beijnen. Population pharmacokinetics of cyclophosphamide and its metabolites 4-hydroxycyclophosphamide, 2-dechloroethylcyclophosphamide, and phosphoramide mustard in a high-dose combination with Thiotepa and Carboplatin.
Therapeutic drug monitoring.
2005 Dec; 27(6):756-65. doi:
10.1097/01.ftd.0000177224.19294.92. [PMID: 16306851] - Milly E de Jonge, Alwin D R Huitema, Sjoerd Rodenhuis, Jos H Beijnen. Sparse sampling design for therapeutic drug monitoring of sequentially administered cyclophosphamide, thiotepa, and carboplatin (CTC).
Therapeutic drug monitoring.
2005 Jun; 27(3):393-402. doi:
10.1097/01.ftd.0000158081.38330.5e. [PMID: 15905813] - Milly E de Jonge, Alwin D R Huitema, Selma M van Dam, Jos H Beijnen, Sjoerd Rodenhuis. Significant induction of cyclophosphamide and thiotepa metabolism by phenytoin.
Cancer chemotherapy and pharmacology.
2005 May; 55(5):507-10. doi:
10.1007/s00280-004-0922-y. [PMID: 15685452] - Milly E de Jonge, Alwin D R Huitema, Annemarie C Tukker, Selma M van Dam, Sjoerd Rodenhuis, Jos H Beijnen. Accuracy, feasibility, and clinical impact of prospective Bayesian pharmacokinetically guided dosing of cyclophosphamide, thiotepa, and carboplatin in high-dose chemotherapy.
Clinical cancer research : an official journal of the American Association for Cancer Research.
2005 Jan; 11(1):273-83. doi:
. [PMID: 15671556] - Monish Jain, Junying Fan, Nesrine Z Baturay, Chul-Hoon Kwon. Sulfonyl-containing aldophosphamide analogues as novel anticancer prodrugs targeted against cyclophosphamide-resistant tumor cell lines.
Journal of medicinal chemistry.
2004 Jul; 47(15):3843-52. doi:
10.1021/jm0304764. [PMID: 15239662] - Milly E de Jonge, Alwin D R Huitema, Sjoerd Rodenhuis, Jos H Beijnen. Integrated Population Pharmacokinetic Model of both cyclophosphamide and thiotepa suggesting a mutual drug-drug interaction.
Journal of pharmacokinetics and pharmacodynamics.
2004 Apr; 31(2):135-56. doi:
10.1023/b:jopa.0000034405.03895.c2. [PMID: 15379382] - Ruolun Qiu, Thomas F Kalhorn, John T Slattery. ABCC2-mediated biliary transport of 4-glutathionylcyclophosphamide and its contribution to elimination of 4-hydroxycyclophosphamide in rat.
The Journal of pharmacology and experimental therapeutics.
2004 Mar; 308(3):1204-12. doi:
10.1124/jpet.103.059105. [PMID: 14617693] - Milly E de Jonge, Selma M van Dam, Michel J X Hillebrand, Hilde Rosing, Alwin D R Huitema, Sjoerd Rodenhuis, Jos H Beijnen. Simultaneous quantification of cyclophosphamide, 4-hydroxycyclophosphamide, N,N',N"-triethylenethiophosphoramide (thiotepa) and N,N',N"-triethylenephosphoramide (tepa) in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.
Journal of mass spectrometry : JMS.
2004 Mar; 39(3):262-71. doi:
10.1002/jms.570. [PMID: 15039933] - M E de Jonge, R A A Mathôt, O Dalesio, A D R Huitema, S Rodenhuis, J H Beijnen. Relationship between irreversible alopecia and exposure to cyclophosphamide, thiotepa and carboplatin (CTC) in high-dose chemotherapy.
Bone marrow transplantation.
2002 Nov; 30(9):593-7. doi:
10.1038/sj.bmt.1703695. [PMID: 12407434] - Milly E De Jonge, Ron A A Mathôt, Selma M Van Dam, Jos H Beijnen, Sjoerd Rodenhuis. Extremely high exposures in an obese patient receiving high-dose cyclophosphamide, thiotepa and carboplatin.
Cancer chemotherapy and pharmacology.
2002 Sep; 50(3):251-5. doi:
10.1007/s00280-002-0494-7. [PMID: 12203108] - Laimonas Griskevicius, Lennart Meurling, Moustapha Hassan. Simple method based on fluorescent detection for the determination of 4-hydroxycyclophosphamide in plasma.
Therapeutic drug monitoring.
2002 Jun; 24(3):405-9. doi:
10.1097/00007691-200206000-00013. [PMID: 12021633] - Eva Kovacs. The in vitro effect of Viscum album (VA) extract on DNA repair of peripheral blood mononuclear cells (PBMC) in cancer patients.
Phytotherapy research : PTR.
2002 Mar; 16(2):143-7. doi:
10.1002/ptr.920. [PMID: 11933116] - C M Dieckhaus, W L Santos, R D Sofia, T L Macdonald. The chemistry, toxicology, and identification in rat and human urine of 4-hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one: a reactive metabolite in felbamate bioactivation.
Chemical research in toxicology.
2001 Aug; 14(8):958-64. doi:
10.1021/tx000139n. [PMID: 11511169] - A D Huitema, R A Mathôt, M M Tibben, S Rodenhuis, J H Beijnen. A mechanism-based pharmacokinetic model for the cytochrome P450 drug-drug interaction between cyclophosphamide and thioTEPA and the autoinduction of cyclophosphamide.
Journal of pharmacokinetics and pharmacodynamics.
2001 Jun; 28(3):211-30. doi:
10.1023/a:1011543508731. [PMID: 11468938] - L Belfayol-Pisanté, L Guillevin, M Tod, F Fauvelle. Pharmacokinetics of cyclophosphamide (CP) and 4-OH-CP/aldophosphamide in systemic vasculitis.
Fundamental & clinical pharmacology.
2000 Jul; 14(4):415-21. doi:
10.1111/j.1472-8206.2000.tb00424.x. [PMID: 11030450] - H A Hahm, D K Armstrong, T L Chen, L Grochow, J Passos-Coelho, S N Goodman, N E Davidson, M J Kennedy. Novobiocin in combination with high-dose chemotherapy for the treatment of advanced breast cancer: a phase 2 study.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.
2000; 6(3A):335-43. doi:
10.1016/s1083-8791(00)70059-0. [PMID: 10905771] - M Hassan, U S Svensson, P Ljungman, B Björkstrand, H Olsson, M Bielenstein, M Abdel-Rehim, C Nilsson, M Johansson, M O Karlsson. A mechanism-based pharmacokinetic-enzyme model for cyclophosphamide autoinduction in breast cancer patients.
British journal of clinical pharmacology.
1999 Nov; 48(5):669-77. doi:
10.1046/j.1365-2125.1999.00090.x. [PMID: 10594468] - M Hassan, C Nilsson, H Olsson, J Lundin, A Osterborg. The influence of interferon-alpha on the pharmacokinetics of cyclophosphamide and its 4-hydroxy metabolite in patients with multiple myeloma.
European journal of haematology.
1999 Sep; 63(3):163-70. doi:
10.1111/j.1600-0609.1999.tb01764.x. [PMID: 10485271] - S Ren, T F Kalhorn, J T Slattery. Inhibition of human aldehyde dehydrogenase 1 by the 4-hydroxycyclophosphamide degradation product acrolein.
Drug metabolism and disposition: the biological fate of chemicals.
1999 Jan; 27(1):133-7. doi:
. [PMID: 9884322] - T L Chen, M J Kennedy, L W Anderson, S B Kiraly, K C Black, O M Colvin, L B Grochow. Nonlinear pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide/aldophosphamide in patients with metastatic breast cancer receiving high-dose chemotherapy followed by autologous bone marrow transplantation.
Drug metabolism and disposition: the biological fate of chemicals.
1997 May; 25(5):544-51. doi:
. [PMID: 9152592] - J T Slattery, T F Kalhorn, G B McDonald, K Lambert, C D Buckner, W I Bensinger, C Anasetti, F R Appelbaum. Conditioning regimen-dependent disposition of cyclophosphamide and hydroxycyclophosphamide in human marrow transplantation patients.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology.
1996 May; 14(5):1484-94. doi:
10.1200/jco.1996.14.5.1484. [PMID: 8622062] - B A Kamen, E Frenkel, O M Colvin. Ifosfamide: should the honeymoon be over?.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology.
1995 Feb; 13(2):307-9. doi:
10.1200/jco.1995.13.2.307. [PMID: 7844590] - L Belfayol, L Guillevin, K Louchahi, O Lortholary, A M Bosio, F Fauvelle. Measurement of 4-hydroxycyclophosphamide in serum by reversed-phase high-performance liquid chromatography.
Journal of chromatography. B, Biomedical applications.
1995 Jan; 663(2):395-9. doi:
10.1016/0378-4347(94)00462-e. [PMID: 7735489] - K K Chan, P S Hong, K Tutsch, D L Trump. Clinical pharmacokinetics of cyclophosphamide and metabolites with and without SR-2508.
Cancer research.
1994 Dec; 54(24):6421-9. doi:
. [PMID: 7987837] - M Johansson, M Bielenstein. Determination of 4-hydroxycyclophosphamide in plasma, as 2,4-dinitrophenylhydrazone derivative of aldophosphamide, by liquid chromatography.
Journal of chromatography. B, Biomedical applications.
1994 Oct; 660(1):111-20. doi:
10.1016/0378-4347(94)00283-5. [PMID: 7858703] - M Untch, B U Sevin, J P Perras, R Angioli, A Baibl, H N Nguyen, R D Hightower, H E Averette. Chemosensitivity to the new anthracycline pirarubicin and other chemotherapeutic agents in primary and recurrent ovarian tumors in vitro.
Gynecologic oncology.
1992 Nov; 47(2):172-8. doi:
10.1016/0090-8258(92)90102-o. [PMID: 1468695] - H N Nguyen, B U Sevin, H E Averette, J Perras, D Donato, M Penalver. The use of ATP bioluminescence assays in selecting a drug screen panel for chemosensitivity testing of uterine cancer cell lines.
Gynecologic oncology.
1992 May; 45(2):185-91. doi:
10.1016/0090-8258(92)90283-o. [PMID: 1592285] - R T Gerhardt, J P Perras, B U Sevin, E Petru, R Ramos, L Guerra, H E Averette. Characterization of in vitro chemosensitivity of perioperative human ovarian malignancies by adenosine triphosphate chemosensitivity assay.
American journal of obstetrics and gynecology.
1991 Aug; 165(2):245-55. doi:
10.1016/0002-9378(91)90075-3. [PMID: 1872324] - P S Hong, A Srigritsanapol, K K Chan. Pharmacokinetics of 4-hydroxycyclophosphamide and metabolites in the rat.
Drug metabolism and disposition: the biological fate of chemicals.
1991 Jan; 19(1):1-7. doi:
. [PMID: 1673381] - S A Little, P E Mirkes. Relationship of DNA damage and embryotoxicity induced by 4-hydroperoxydechlorocyclophosphamide in postimplantation rat embryos.
Teratology.
1990 Feb; 41(2):223-31. doi:
10.1002/tera.1420410214. [PMID: 2321166] - P S Hong, K K Chan. Analysis of 4-hydroxycyclophosphamide by gas chromatography-mass spectrometry in plasma.
Journal of chromatography.
1989 Oct; 495(?):131-8. doi:
10.1016/s0378-4347(00)82616-x. [PMID: 2613798] - C H Kwon, R F Borch. Effects of N-substitution on the activation mechanisms of 4-hydroxycyclophosphamide analogues.
Journal of medicinal chemistry.
1989 Jul; 32(7):1491-6. doi:
10.1021/jm00127a016. [PMID: 2738883] - R F Struck, D S Alberts, K Horne, J G Phillips, Y M Peng, D J Roe. Plasma pharmacokinetics of cyclophosphamide and its cytotoxic metabolites after intravenous versus oral administration in a randomized, crossover trial.
Cancer research.
1987 May; 47(10):2723-6. doi:
NULL. [PMID: 3552204] - C H Kwon, K Maddison, L LoCastro, R F Borch. Accelerated decomposition of 4-hydroxycyclophosphamide by human serum albumin.
Cancer research.
1987 Mar; 47(6):1505-8. doi:
. [PMID: 3815352] - S Rosenow, K L Kooistra, G Powis, R A Van Dyke. Increased toxicity of the antitumor drug cyclophosphamide in mice in the presence of the volatile anesthetic agent halothane.
Cancer chemotherapy and pharmacology.
1986; 16(1):35-42. doi:
10.1007/bf00255283. [PMID: 3940218] - N E Sladek, D Doeden, J F Powers, W Krivit. Plasma concentrations of 4-hydroxycyclophosphamide and phosphoramide mustard in patients repeatedly given high doses of cyclophosphamide in preparation for bone marrow transplantation.
Cancer treatment reports.
1984 Oct; 68(10):1247-54. doi:
. [PMID: 6395951] - J F Powers, N E Sladek. Cytotoxic activity relative to 4-hydroxycyclophosphamide and phosphoramide mustard concentrations in the plasma of cyclophosphamide-treated rats.
Cancer research.
1983 Mar; 43(3):1101-6. doi:
NULL. [PMID: 6825082] - N E Sladek, P C Smith, P M Bratt, J E Low, J F Powers, R F Borch, J R Coveney. Influence of diuretics on urinary general base catalytic activity and cyclophosphamide-induced bladder toxicity.
Cancer treatment reports.
1982 Nov; 66(11):1889-1900. doi:
. [PMID: 7139634] - J E Low, R F Borch, N E Sladek. Conversion of 4-hydroperoxycyclophosphamide and 4-hydroxycyclophosphamide to phosphoramide mustard and acrolein mediated by bifunctional catalysis.
Cancer research.
1982 Mar; 42(3):830-7. doi:
. [PMID: 7059981] - N Brock, J Pohl, J Stekar. Detoxification of urotoxic oxazaphosphorines by sulfhydryl compounds.
Journal of cancer research and clinical oncology.
1981; 100(3):311-20. doi:
10.1007/bf00410691. [PMID: 6792207]
