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  • 1
    Electronic Resource
    Electronic Resource
    Effect of the mutation of tyrosine 713 in p93c-fes on its catalytic activity and ability to promote myeloid differentiation in K562 cells (1993)
    s.l. : American Chemical Society
    Biochemistry 32 (1993), S. 6995-7001 
    Details
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/bi00078a026
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Oxidative destruction of erythrocyte ghost membranes catalyzed by the doxorubicin-iron complex (1982)
    s.l. : American Chemical Society
    Biochemistry 21 (1982), S. 1707-1713 
    Details
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/bi00537a001
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Steady-state plasma concentrations and effects of taxol for a 250 mg/m2 dose in combination with granulocyte-colony stimulating factor in patients with ovarian cancer (1993)
    Springer
    Cancer chemotherapy and pharmacology 33 (1993), S. 48-52 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Taxol, a natural product initially isolated from the stem bark of the western yewTaxus brevifolia, is undergoing phase II and III evaluation due to its reported activity against a variety of tumors. Previous studies have described correlations between plasma concentrations and toxicity when taxol is given (a) at lower doses, (b) for shorter infusion times, and (c) without granulocyte-colonystimulating factor. Because the 24-h infusion schedule is most commonly used in current clinical trials, we attempted to correlate steady-state plasma concentrations of taxol achieved with a 24-h continuous i.v. infusion with toxicities and responses. Plasma samples from 48 refractory ovarian cancer patients were obtained 1–2 h prior to the end of the first taxol infusion. Taxol concentrations were measured by high-performance liquid chromatography (HPLC). Interpatient variation of taxol plasma concentrations was small (mean±SD, 0.85±0.21 μM. Total taxol body clearance was 256±72 ml min−1m−2 (mean±SD). Taxol plasma protein binding was 88.4%±1.3% (mean±SD,n=9). Grade 3–4 hematologic toxicity, mainly leukopenia, occurred in 92% of the patients. The leukopenia was transient and did not warrant a reduction in the dose of taxol. Grade 3–4 nonhematologic toxicity occurred in 8% of the patients. No severe hypersensitivity reaction or grade 3–4 neurotoxicity was observed. Correlations of plasma concentrations and toxicities were not feasible due to the high frequency of hematologic effects and the low frequency of nonhematologic toxicity. The low degree of interpatient variation in plasma concentrations hindered the development of correlations with response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686022
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Metabolism of taxol by human and rat liver in vitro: A screen for drug interactions and interspecies differences (1995)
    Springer
    Cancer chemotherapy and pharmacology 36 (1995), S. 107-114 
    Details
    ISSN: 1432-0843
    Keywords: Drug metabolism ; Species differences ; Drug interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Human liver slices, human liver microsomes, and rat liver microsomes were used to investigate the metabolism of3H-taxol. The effects of drugs frequently coadministered with taxol and the effects of several cytochrome P450 system probes were studied. In all, 16 compounds were screened. After incubation with liver slices or with microsomal protein,3H-taxol was converted into several radioactive species resolved by HPLC. There were qualitative and quantitative species differences in the metabolism of taxol. The pattern of metabolism was similar for both human-derived preparations, with 6α-hydroxytaxol being the major metabolite peak. In drug interaction studies performed with human liver microsomes, cimetidine 80 μM, and diphenhydramine 200 μM, had little or no effect on 6α-hydroxytaxol formation. Quinidine, ketoconazole, dexamethasone and Cremophor EL inhibited 6α-hydroxytaxol formation with IC50 values of 36 μM, 37 μM, 16 μM and 1 μl/ml, respectively, but these concentrations exceed the usual clinical range. Cremophor EL also inhibited microsomal metabolism of taxol, but at 2 μl/ml it had little or no effect on 6α-hydroxytaxol production by human liver slices. These results suggest that: (1) taxol is metabolized by the cytochrome P450 system; (2) taxol metabolism is different in humans than in rats; (3) taxol metabolism in humans is unlikely to be altered by cimetidine, dexamethasone, or diphenhydramine, drugs regularly coadministered with taxol; (4) taxol metabolism can be indirectly affected by Cremophor EL, the formulation vehicle; (5) taxol metabolism may be altered by concentrations of ketoconazole achievable in humans only at very high doses; and (6) taxol metabolism and drug interaction studies of clinical relevance can be performed in vitro with human liver microsomes and human liver slices, but not with rat liver preparations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689193
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    Metabolism of taxol by human and rat liver in vitro: A screen for drug interactions and interspecies differences (1995)
    Springer
    Cancer chemotherapy and pharmacology 36 (1995), S. 107-114 
    Details
    ISSN: 1432-0843
    Keywords: Key words Drug metabolism ; Species differences ; Drug interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Human liver slices, human liver microsomes, and rat liver microsomes were used to investigate the metabolism of 3H-taxol. The effects of drugs frequently coadministered with taxol and the effects of several cytochrome P450 system probes were studied. In all, 16 compounds were screened. After incubation with liver slices or with microsomal protein, 3H-taxol was converted into several radioactive species resolved by HPLC. There were qualitative and quantitative species differences in the metabolism of taxol. The pattern of metabolism was similar for both human-derived preparations, with 6α-hydroxytaxol being the major metabolite peak. In drug interaction studies performed with human liver microsomes, cimetidine 80 μM, and diphenhydramine 200 μM, had little or no effect on 6α-hydroxytaxol formation. Quinidine, ketoconazole, dexamethasone and Cremophor EL inhibited 6α-hydroxytaxol formation with IC50 values of 36 μM, 37 μM, 16 μM and 1 μl/ml, respectively, but these concentrations exceed the usual clinical range. Cremophor EL also inhibited microsomal metabolism of taxol, but at 2 μl/ml it had little or no effect on 6α-hydroxytaxol production by human liver slices. These results suggest that: (1) taxol is metabolized by the cytochrome P450 system; (2) taxol metabolism is different in humans than in rats; (3) taxol metabolism in humans is unlikely to be altered by cimetidine, dexamethasone, or diphenhydramine, drugs regularly coadministered with taxol; (4) taxol metabolism can be indirectly affected by Cremophor EL, the formulation vehicle; (5) taxol metabolism may be altered by concentrations of ketoconazole achievable in humans only at very high doses; and (6) taxol metabolism and drug interaction studies of clinical relevance can be performed in vitro with human liver microsomes and human liver slices, but not with rat liver preparations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689193
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    Paper (German National Licenses)
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  • 6
    Electronic Resource
    Electronic Resource
    Phase I and pharmacokinetic study of tiazofurin (TCAR, NSC 286193) administered by continuous infusion (1985)
    Springer
    Investigational new drugs 3 (1985), S. 349-355 
    Details
    ISSN: 1573-0646
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Tiazofurin (2-β-D-ribofuranosylthiazole-4-carboxamide, TCAR) is a synthetic C-nucleoside that demonstrated significant in vivo activity against a variety of animal tumors as well as in vitro activity against human tumor-derived cell lines. Thirteen patients were treated with TCAR administered as a 5-day continuous infusion in this Phase I trial. Seventeen complete cycles were administered in three dose levels ranging from 550 to 1450 mg/M2. Dose-limiting toxicities were myelosuppression and neurotoxicity including severe lethargy. Other toxicities including superficial skin peeling, myalgias, and tearing were seen at all doses. One patient had chest pain on day 4 resulting in stopping the drug, however, there was no evidence of cardiac or pericardial disease. Uric acid levels rose within one day in the absence of allopurinol treatment. There were no treatment related deaths. HPLC measurement of drug levels demonstrated steady-state plasma levels during the infusion, and a half-life following the infusion of 7.7 ± 0.6 hours. Minor abnormalities in renal function were associated with dramatic changes in pharmacokinetics and toxicity. No clinical responses were observed in this trial.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00170757
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    Paper (German National Licenses)
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