Disease relevance of Triethylenephosphoramide

• The AUC and total body clearance of thioTEPA, but not of TEPA, were closely correlated with neutrophil but not platelet toxicity [1].
• Linear and cyclic polyether derivatives of N,N:N',N':N'',N''-tri-1, 2-ethanediylphosphoric triamide (TEPA) and N,N:N',N':N'',N''-tri-1,2-ethanediylphosphorothioic triamide (thio-TEPA) are synthesized and evaluated for their antineoplastic activity against the murine lymphocytic leukemia P388 [2].
• The frequency of sister chromatid exchanges (SCE) and chromosome aberrations and the dynamics of cell division in peripheral blood lymphocytes of four patients with Fanconi's anemia were studied after in vitro exposure to alkylating agents TEPA and mitomycin [3].
• Similar types of chromosomal aberration were found, but the effect of ECHH was 4-5 times lower than that of TEPA [4].
• Long-term pharmacokinetics of thio-TEPA, TEPA and total alkylating activity following i.v. bolus administration of thio-TEPA in ovarian cancer patients [5].

High impact information on Triethylenephosphoramide

• An attempt was made to unravel the metabolic profile of the alkylating agent N,N',N''-triethylenethiophosphoramide (thioTEPA). thioTEPA and its metabolite N,N',N-triethylenephosphoramide (TEPA) were quantified in urine of treated patients by gas chromatography with selective nitrogen/phosphorous detection [6].
• The pharmacokinetics of thiotepa and its principal metabolite TEPA were studied in 23 patients [7].
• The AUC of TEPA was lower than that previously observed [7].
• Although these rates are low compared to those catalyzed by phenobarbital-induced liver microsomes (3.5 nmol TEPA/min/mg), they are sufficient to contribute to the systemic metabolism of this drug [8].
• Alkaline elution studies of L1210 cells that had been incubated with TEPA, alone or in the presence of microsomes and NADPH, demonstrated an elution pattern identical to that produced by thioTEPA in the presence of microsomes and NADPH [9].

Chemical compound and disease context of Triethylenephosphoramide

• The severity of the platelet toxicity was correlated with the AUC of thiotepa, but not with that of TEPA [7].
• Banding technique used for the detection of chromosomal aberrations induced by radiation and alkylating agents TEPA and epichlorohydrin [10].

Biological context of Triethylenephosphoramide

• SCE frequency was significantly increased even after very low doses of mutagens, while chromosome aberrations were significantly increased only after high doses (0.160 micrograms/ml mitomycin and 10(-5) M TEPA) [3].
• The results of dominant-lethal and bone-marrow cytogenetic studies in mice after consumption of drinking water containing 1000 mg of 5-NFA/1 for 12 weeks and dosed subsequently with TEPA suggests that 5-NFA has some antimutagenic activity [11].
• Influence of the tissue distribution of ThioTEPA and its metabolite, TEPA, on the response of murine colon tumours [12].
• After exposures to TEPA and ECHH, 10.9% of aberrations were undectable in G0 and 3.3% in G1S and G2 phases [10].
• We found that Thio-TEPA is approximately two-fold more active than TEPA in arresting cell growth (IC50 = 2.8 microM for TEPA and 1.5 microM for Thio-TEPA) [13].

Anatomical context of Triethylenephosphoramide

• The antineoplastic agents N,N',N''-triethylenethiophosphoramide (thioTEPA) and N,N',N''-triethylenephosphoramide (TEPA) were studied for their interaction with the DNA of L1210 cells in the presence and absence of rat hepatic microsomes and NADPH [9].
• One of these cell lines proved hypersensitive to TEPA, whereas the other was no more sensitive to TEPA than were lymphoblasts from normal humans [9].
• We conclude that Cudt containing TEPA depletes exocrine tissue and facilitates pancreas digestion for successful transplantation of islets into the portal system [14].
• Significantly more eggs were fertilized by untreated than by TEPA-treated spermatozoa [15].
• For CFU-GM and BFU-E growth in vitro, the IC50(s) of thioTEPA were 83 ng/ml and 16 ng/ml, respectively, and the IC50(s) of TEPA were 141 ng/ml and 47 ng/ml, respectively [16].

Associations of Triethylenephosphoramide with other chemical compounds

• Depletion of hepatic P450 IIC11 by cisplatin treatment of adult male rats led to a 70% reduction of TEPA formation catalyzed by the isolated liver microsomes, suggesting that cisplatin may influence thio-TEPA pharmacokinetics when these two drugs are given in combination [8].
• Mutagenic effect of epichlorohydrin. I. Testing on human lymphocytes in vitro in comparison with TEPA [4].
• 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 [17].
• AIMS: To study the population pharmacokinetics of thioTEPA and its main metabolite TEPA in patients receiving high-dose chemotherapy consisting of thioTEPA (80-120 mg x m(-2) x day(-1)), cyclophosphamide (1000-1500 mg x m(-2) x day(-1)) and carboplatin (265-400 mg x m(-2) x day(-1)) for 4 days [18].
• The method described is based on the reaction of triethylenethiophosphoramide (ThioTEPA) and triethylenephosphoramide (TEPA), through their ethyleneimine groups, with sodium sulphide, taurine and o-phthalaldehyde to give fluorescent products, and separation of the derivatives by reversed-phase high-performance liquid chromatography [19].

Gene context of Triethylenephosphoramide

• MUC5AC and MUC5B mucin secretion was measured by an enzyme-linked immunosorbent assay (ELISA) using a specific monoclonal antibody NCL-HGM-45M1 and polyclonal antiserum TEPA, respectively [20].
• Cytochrome P450 isozymes 3A4 and 2B6 are involved in the in vitro human metabolism of thiotepa to TEPA [21].
• Oxidation of thio-TEPA to TEPA was also catalyzed by purified P-450 PB-4 (Km (app) 19 microM; Vmax (app) = 11 mol thio-TEPA metabolized/min/mol P-450 PB-4) following reconstitution of the cytochrome with NADPH P-450 reductase in a lipid environment [22].
• After extraction of ThioTEPA and its metabolite, triethylenephosphoramide (TEPA), from plasma using Sep-Pak C18 cartridges, the compounds were separated by capillary chromatography, detected using a nitrogen detector and quantified by reference to an internal standard, hexaethylphosphoramide [23].
• In both groups early recovery of normal activities was noted, after a mean of respectively 13.6 days (TAPP) and 12.9 days (TEPA) [24].

Analytical, diagnostic and therapeutic context of Triethylenephosphoramide

• Plasma concentrations of thioTEPA and its major active metabolite triethylenephosphoramide (TEPA) were measured by gas chromatography [1].
• Population pharmacokinetics of thioTEPA and its active metabolite TEPA in patients undergoing high-dose chemotherapy [18].
• Since, IOV of both thioTEPA and TEPA was equal to or smaller than IIV, therapeutic drug monitoring based on data of previous courses may be meaningful using this population model [18].

References