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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 53 (1983), S. 33-39 
    ISSN: 1432-0738
    Keywords: Diphenhydramine ; Cardiotoxicity ; Antihistaminics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A fatal monointoxication with diphenhydramine in a male 28 year old is reported. The patient went into hyperpyrexia and tachycardia and died from sudden cardiac arrest. Hemorrhagic pulmonary edema and renal shock were the most prominent pathomorphological findings. At the time of death, the concentration of diphenhydramine was 5 mg/l plasma and was particularly high in the lungs (55 mg/kg) and kidneys (50mg/kg).
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-0646
    Keywords: phase I ; dextran-conjugated doxorubicin ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Coupling of anthracyclines to high-molecular-weight carriers may alter drug disposition and improve antitumor effects. We have performed a clinical phase I trial of doxorubicin coupled to dextran (70000 m.w.). The drug was administered as single dose i.v. every 21–28 days. Thirteen patients have received a total of 24 courses (median 2; range 1–3). At the starting dose of 40 mg/m2 doxorubicin equivalent (DOXeq), WHO grade IV thrombocytopenia was noted in 2/2 patients. WHO grade IV hepatotoxicity and WHO grade III cardiotoxicity were noted in a patient with preexisting heart disease. Five patients were treated with 12.5 mg/m2 DOXeq. Maximal toxicity at this dose level was WHO grade III thrombocytopenia and local phlebitis (WHO grade II) in 1/5 patients, elevation of alkaline phosphatase (WHO grade III) and WHO grade III vomiting in another patient. Subsequently, five patients received 20 mg/m2 DOXeq. Hepatotoxicity was noted in 5/5 patients (1 × WHO grade IV, 1 × WHO grade III). Thrombocytopenia was noted in 3/5 patients (1 × WHO grade IV, 2 × WHO grade III). At 12.5 mg/m2 DOXeq, a patient diagnosed with a malignant fibrous histiocytoma had stable disease for 4 months. Pharmacokinetic analyses of total and free doxorubicin were performed in plasma and urine. The maximum peak plasma concentration (ppc) for total DOX was 12.3 μg/ml at 40 mg/m2 DOXeq. The area under the plasma concentration time curve (AUC) ranged from 28.83–80.21 μg/ml*h with dose-dependent elimination half lives (t1/2α: 0.02–0.87 h;1/2β: 2.69–11.58 h;1/2γ: 41.44–136.58 h). We conclude that the maximal tolerated dose (MTD) of AD-70 using this schedule is 40 mg/m2 DOXeq. The recommended dose for clinical phase II studies is 12.5 mg/m2 DOXeq.
    Type of Medium: Electronic Resource
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