Oxazaphosphorine metabolites

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WebMay 6, 2010 · Importance of the field: The oxazaphosphorines (cyclophosphamide, ifosfamide and trofosfamide) are widely used in clinical practice for their antitumor and … WebApr 1, 2012 · 2.1. Cytochrome P450. Prototypical oxazaphosphorine cytostatics such as CPA and IFO are chemically and pharmacologically inactive transport forms of alkylating nitrogen mustards that are biotransformed to their active forms predominantly in the liver 47; 48.As one of the key mechanisms of action, hepatic metabolism of CPA, has been …

Metabolism and Pharmacokinetics of Oxazaphosphorines

WebThe formation and rapid urinary excretion of conjugates of the activated (4-hydroxylated) oxazaphosphorine metabolites with mesna has been suggested as the pharmacological … WebThe P450 metabolites of CPA and IFA, CA (formed by the N-dechloroethylation pathway) and acrolein (formed by the 4-hydroxylation pathway), were determined in parallel using a single incubation tube [27]. Incubations were carried out for 30 min in a total volume of 100 mL, and included 50 mM potassium phosphate buffer, pH 7.4, 0.1 hwatime logo

Metabolism and transport of oxazphosphorines and the clinical ...

WebOxazaphosphorine metabolism and transport have a major impact on pharmacokinetic variability, pharmacokinetic-pharmacodynamic relationship, toxicity, resistance, and drug … WebApr 1, 2015 · (Total dose = 160% (w/w) of the oxazaphosphorine dose). This larger dose is recommended in children, in patients whose urothelium may be damaged from previous … WebOXAZAPHOSPHORINE METABOLISM BY THE HUMAN CYTOCHROME P450s AND SOME COMMONLY EXPRESSED P450 POLYMORPHIC VARIANTS by Diane M. Calinski A … h watkins father im coming home

Oxazaphosphorines: new therapeutic strategies for an old …

Cyclophosphamide and related anticancer drugs - ScienceDirect

WebThe initial metabolism of the oxazaphosphorine cytostatic ifosfamide (IF) consists of two different pathways: ring oxidation at carbon-4 forms the cytostatically active metabolite 4-hydroxyifosfamide (4-OH-IF, “activated ifosfamide”), whereas side-chain oxidation with liberation of the presumably neurotoxic compound chloroacetaldehyde (CAA) that may … WebIn order to reduce the oxazophosphorine-related urothelial toxicity, sodium mercaptoethane sulphonate (mesna) is used in different schedules following the administration of ifosfamide. The proposed mechanism of mesna activity is the binding of toxic oxazaphosphorine metabolites such as acrolein in the urine of the patients. hwat hank hillWebMay 1, 2004 · Cyclophosphamide (CPA) and ifosfamide (IFA) are oxazaphosphorine anticancer prodrugs metabolized by two alternative cytochrome P450 (P450) pathways, drug activation by 4-hydroxylation and drug inactivation by N -dechloroethylation, which generates the neurotoxic and nephrotoxic byproduct chloroacetaldehyde. maschinentyp definition

"http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Mesna_monograph_1Nov07.pdf " - Oxazaphosphorine metabolites

Oxazaphosphorine metabolites

Metabolism and transport of oxazaphosphorines and the

WebThe active metabolites of cyclophosphamide are highly protein bound and distributed to all tissues, are assumed to cross the placenta and are known to be present in breast milk. … WebMar 1, 2024 · On the basis of the discovery that the proapoptotic aldehyde 3-hydroxypropanal is a cyclophosphamide metabolite, a novel mechanism of action of oxazaphosphorine cytostatics is presented and ...

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WebOXAZAPHOSPHORINE METABOLISM BY THE HUMAN CYTOCHROME P450s AND SOME COMMONLY EXPRESSED P450 POLYMORPHIC VARIANTS by Diane M. Calinski A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Pharmacology) in the University of Michigan 2013 Doctoral Committee: … WebMay 1, 2002 · CAA, a byproduct of oxazaphosphorine metabolism, displayed appreciable cytotoxic activity in cell culture (EC 50 ϳ 2.5 M, compared with EC 50 values of 3-5 M for the 4-hydroxy derivatives of CPA ...

WebMay 1, 2010 · The metabolism of oxazaphosphorines involves cytochrome P450 biotransformations, leading to highly reactive metabolites such as acrolein and … WebThe concentrations of the parent oxazaphosphorine and its principal metabolites were measured simultaneously in the plasma and CSF of 25 children. Twenty-one patients received CP for the treatment of either acute lymphoblastic leukemia, non-Hodgkin's lymphoma, or medulloblastoma, and 4 children received IF for the treatment of …

WebThat the oxazaphosphorines continue to be the subject of intensive investigation over 30 years after their introduction into clinical practice is partly because of their antitumour activity. The 2 most commonly used oxazaphosphorines are cyclophosphamide and ifosfamide, although other bifunctional mustard analogues continue to be investigated. … WebMafosfamide (4-thioethane sulfonic acid salt of 4-hydroxy-cyclophosphamide, MAF) belongs to a new generation of the oxazaphosphorine agents. MAF is a cyclophosphamide analog which spontaneously degrades to 4-hydroxy-cyclophosphamide. The effects of

WebSep 28, 2024 · In vitro, toxic acrolein is formed during the formation of the cytotoxic metabolite phosphoreamidemustard (PAM), whereas in vivo proapoptotic hydroxypropanal (HPA) is formed. The CP metabolites formed in sequence 4-hydroxycyclophosphamide (OHCP) are the main cause of toxicity, aldophosphamide (ALDO) is the pharmacologically …

Webthe oxazaphosphorine metabolites. After oral or intravenous administration, mesna undergoes rapid oxidation in the plasma to dimesna. Only a small portion of the dose remains in the circulation as the physiologically active compound. Both mesna and dimesna are very hydrophilic and therefore remain in the intravascular compartment, maschinentransport speditionWebJan 1, 1989 · Abstract. The development of the oxazaphosphorine cytostatics cyclophosphamide, ifosfamide, and trofosfamide was based on the idea of applying the transport form/active form principle to the highly reactive nitrogen mustard group. A critical analysis and synopsis of the available results and knowledge will include examination of … hwa to groningenWebJul 1, 2005 · Oxazaphosphorine metabolism is affected by a number of factors associated with the drugs (e.g., dosage, route of administration, chirality, and drug combination) and patients (e.g., age, gender ... hwa thong bags industries sdn bhdWebCyclophosphamide is an oxazaphosphorine that contributes alkyl groups to DNA, forming covalent linkages. It depletes T and B cells and suppresses antibody production. It is metabolized to 4-hydroxycyclophosphamide and its tautomer aldophosphamide by liver … Yanfeng Wang, Weiyang He, in The Liver, 2024. Introduction of mitochondria … maschinen und apparatebau rathenowWebThe metabolism of oxazaphosphorines is auto-inducible, with the activation of the orphan nuclear receptor pregnane X receptor (PXR) being the major mechanism. Oxazaphosphorine metabolism is affected by a number of factors associated with the drugs (e.g., dosage, route of administration, chirality, and drug combination) and patients (e.g., age ... hwato acupuncture machineWebThe active metabolites of cyclophosphamide are highly protein bound and distributed to all tissues, are assumed to cross the placenta and are known to be present in breast milk. [40] It is specifically in the oxazaphosphorine group of medications. [41] hwat inspired jerry spinelli to be a writeWebJan 1, 2005 · Oxazaphosphorine metabolism and transport have a major impact on pharmacokinetic variability, pharmacokinetic-pharmacodynamic relationship, toxicity, resistance, and drug interactions since the drug-metabolizing enzymes and drug transporters involved are key determinants of the pharmacokinetics and … hwato needles