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  • 1
    Electronic Resource
    Electronic Resource
    Preclinical Antitumor Activity and Pharmacokinetics of Irinotecan (CPT-11) in Tumor-bearing Mice (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 803 (1996), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1996.tb26386.x
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  • 2
    Electronic Resource
    Electronic Resource
    Early-phase pharmacokinetics of doxorubicin in non-hodgkin lymphoma patients (1983)
    Springer
    Cancer chemotherapy and pharmacology 10 (1983), S. 115-119 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The early-phase (20 min) pharmacokinetics of doxonrubicin was studied in 18 patients suffering from non-Hodgkin lymphoma and receiving various schedules and/or dosages of the drug. This pharmacokinetics was time-dependent in most patients over a 2-week interval: repeating similar doses in patients leads to a decrease of the drug exposure due to a decrease of the half-life and/or to a decrease of the extrapolation to 0 time (intercept parameter). The pharmacokinetics was generally time-independent within a 6-h interval in most patients. During this time interval, the kinetics was not linear: increasing the dose by large proportions does not lead to a proportional increase of drug exposure. This time- and dose-dependence of doxorubicin pharmacokinetics makes it very difficult to monitor the treatments according to the individual pharmacokinetic patterns of patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00446222
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  • 3
    Electronic Resource
    Electronic Resource
    Hepatic extraction, metabolism and biliary excretion of doxorubicin in the isolated prefused rat liver (1987)
    Springer
    Cancer chemotherapy and pharmacology 19 (1987), S. 240-245 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The hepatic extraction, metabolism, and biliary excretion of doxorubicin (DX) were studied in the isolated perfused rat liver. Three doses of DX equivalent to 2, 20, and 100 mg/kg in rats were studied over a period of 3 h after bolus injection into the reservoir. DX and metabolites concentration in perfusate, bile, and liver were determined by high-pressure liquid chromatography. The hepatic extraction ratio was low (〈0.24) and decreased progressively over the 3 h. The hepatic extraction and clearance were significantly lower at the highest dose. Doxorubicinol (DX-OL) was the only metabolite detected in the perfusate, accounting for less than 4% of the total AUC. Thirty-one to thirty-three percent of the dose was excreted into bile over 3 h as unchanged DX. This was reduced to 22% at the highest dose. Only 0.35%–1.33% of the dose was excreted as DX-OL. DX aglycones were found only in the liver, where they represented 20%–30% of the total fluorescence at 3 h. In conclusion, in this model DX has a low extraction ratio, is poorly metabolized and extensively excreted into bile.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00252979
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  • 4
    Electronic Resource
    Electronic Resource
    Antitumor activity of intoplicine (RP 60475, NSC 645008), a new benzo-pyrido-indole: evaluation against solid tumors and leukemias in mice (1993)
    Springer
    Investigational new drugs 11 (1993), S. 263-277 
    Details
    ISSN: 1573-0646
    Keywords: RP 60475 ; intoplicine ; transplantable tumors of mice ; antitumor activity ; DNA topoisomerase inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Intoplicine (RP 60475, NSC 645008) is a new 7H-benzo[e]pyrido[4,3-b] indole derivative which interacts with DNA and inhibits both topoisomerases I and II.In vitro it was found cytotoxic against various cell types with greater cytotoxicity towards solid tumor cells. We report here the anticancer activity of RP 60475 against a variety of transplantable tumors of mice, and also its cross-resistance profile in leukemias. The end points used were % T/C (median tumor weight of the Treated over the Control × 100) and logCK (log10 cell kill total). RP 60475 administered i.v. was found schedule-independent with a peak plasma level problem. It had a good therapeutic index and host recovery usually occurred 7.5 days post last treatment. RP 60475 was found to be highly active against early stage colon 38 (T/C=0%, 2.9 logCK) and could induce 5/5 complete regressions of advanced stage tumor. It was found active against colon adenocarcinoma 51 (T/C=3.6%, 1.9 logCK) and colon carcinoma 26 (T/C=11.7%, 1.2 logCK). Most of the mammary adenocarcinomas were found very responsive, MA16/C (T/C=0%, 2.8 logCK), MA14/A (T/C=0%, 1.4 logCK), MA13/C (T/C=0%, 3.1 log CK) and MA44 (T/C=34%). Excellent activity was also observed against early stage pancreatic ductal adenocarcinoma 03 (T/C=0%) and RP 60475 could achieve 5/5 complete regressions of upstaged tumor. Activity was also obtained on Glasgow osteogenic sarcoma (T/C=0%, 3.3 logCK), on B16 melanoma (T/C=14%, 1.3 logCK) and to a lesser extent on Lewis lung carcinoma (T/C=33.2%). Evaluation of RP 60475 against leukemia sublines with acquired resistance, revealed that L1210/cisplatin and L1210/BCNU were not cross-resistant to RP 60475 whereas P388/vincristine was partially cross-resistant to RP 60475 and P388/doxorubicin was cross-resistant to RP 60475. Based on RP 60475 broad activity against transplantable tumors of mice, its effectiveness against some resistant sublines, its original mechanism of action and its acceptable toxicological profile, this compound was selected for clinical trials.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00874425
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    Paper (German National Licenses)
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