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Therapeutic Drug Monitoring 1989The pharmacokinetics of daunorubicin and doxorubicin were studied in plasma and leukemic cells from 16 patients with acute nonlymphoblastic leukemia during 19 courses of...
The pharmacokinetics of daunorubicin and doxorubicin were studied in plasma and leukemic cells from 16 patients with acute nonlymphoblastic leukemia during 19 courses of treatment with the unconjugated or DNA-conjugated drugs. Daunorubicin and doxorubicin are high-clearance drugs with very high apparent volumes of distribution, indicating a pronounced tissue affinity. This was more pronounced in the case of doxorubicin and may explain the reduced cardiotoxicity of the DNA-complexes. Daunorubicin reached higher intracellular peak concentrations than doxorubicin, but the latter drug was retained much longer. The cell/plasma concentration ratio was higher for daunorubicin than for its reduced metabolite daunorubicinol. No doxorubicinol was found intracellularly. The observed differences in cellular pharmacokinetics between daunorubicin and doxorubicin may explain the difference between the clinical activity spectras of these two drugs. DNA-conjugation did not markedly modify the uptake of daunorubicin in the leukemic cells, whereas the mean intracellular accumulation of doxorubicin was 60% higher when the drug was administered as a DNA-conjugate. This may enhance the selectivity of doxorubicin in the treatment of acute leukemia.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cytarabine; DNA; DNA Adducts; Daunorubicin; Doxorubicin; Humans; Leukemia, Myeloid, Acute; Metabolic Clearance Rate
PubMed: 2718219
DOI: 10.1097/00007691-198903000-00004 -
Anticancer Research Jul 2012Oxazolinodoxorubicin, a doxorubicin analog with a modified daunosamine moiety was synthesized. The properties of this compound and the parent doxorubicin were compared....
Oxazolinodoxorubicin, a doxorubicin analog with a modified daunosamine moiety was synthesized. The properties of this compound and the parent doxorubicin were compared. The cytotoxicity in vitro studies against several human tumor cell lines (PC-3, MCF-7, SW707, HL-60, RPMI 8226, ACHN) showed higher antiproliferative potency for this new compound. Moreover, its ability to completely overcome the drug resistance of cancer cells in vitro was revealed (LoVo, LoVo/DX, MES-SA, MES-SA/DX5, HL-60, HL-60/Vinc, HL-60/MX2 cell lines). Cellular uptake analyzed on HL-60 and HL-60/MX2 cells, demonstrated higher penetration levels of oxazolinodoxorubicin compared to that of doxorubicin. In animal experiments, general toxicity of oxazolinodoxorubicin was lower than that observed for doxorubicin. Furthermore, similar antitumor effects was observed in NOD/SCID mice bearing resistant HL-60/Vinc leukemia tumor and in mice treated with the new or parent compounds. The presented results suggest that oxazolinodoxorubicin is a new anthracycline with an advantageous biological activity profile.
Topics: Animals; Antibiotics, Antineoplastic; Body Weight; Cell Line, Tumor; Daunorubicin; Doxorubicin; Female; HL-60 Cells; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Mice, Inbred NOD; Mice, SCID; Xenograft Model Antitumor Assays
PubMed: 22753760
DOI: No ID Found -
Investigational New Drugs 1994We have completed a phase I and pharmacology study of liposomally-encapsulated daunorubicin (DaunoXome). Of 32 patients entered, 30 were evaluable. No toxicity was... (Clinical Trial)
Clinical Trial
We have completed a phase I and pharmacology study of liposomally-encapsulated daunorubicin (DaunoXome). Of 32 patients entered, 30 were evaluable. No toxicity was encountered at the initial dose-escalation steps from 10 to 60 mg/m2. At 80 mg/m2, two patients manifested grade 2 neutropenia. At least grade 3 neutropenia occurred in all patients receiving 120 mg/m2. Alopecia and subjective intolerance were mild. Cardiotoxicity was not observed except for an episode of arrhythmia in a patient with lung cancer and prior radiation. Only one minor objective response was observed in this population of refractory solid tumors. Pharmacokinetics differed from those of the free drug with no detection of daunorubicinol. We recommend future phase II studies with a dose of 100 mg/m2 in previously treated and 120 mg/m2 of DaunoXome in previously untreated patients with solid tumors.
Topics: Adult; Aged; Daunorubicin; Drug Carriers; Female; Hematologic Diseases; Humans; Liposomes; Male; Middle Aged
PubMed: 7860226
DOI: 10.1007/BF00874439 -
BMC Cancer Sep 2023Recent achievements in cancer therapy are the use of alternating electrical fields at intermediate frequencies (100-300 kHz) and low intensities (1-3 V/cm), which...
BACKGROUND
Recent achievements in cancer therapy are the use of alternating electrical fields at intermediate frequencies (100-300 kHz) and low intensities (1-3 V/cm), which specifically target cell proliferation while affecting different cellular activities depending on the frequency used.
METHODS
In this article, we examine the effect of electric fields on spherical suspended cells and propose the combination of Daunorubicin, a chemotherapy agent widely used in the treatment of acute myeloid leukemia, with electric field exposure. U937 cells were subjected to an electric field with a frequency of 200 kHz and an intensity of 0.75 V/cm, or to a combination of Daunorubicin and electric field exposure, resulting in a significant reduction in cell proliferation. Furthermore, the application of an electric field to U937 cells increased Daunorubicin uptake.
RESULTS
Apoptosis and DNA damage were induced by the electric field or in conjunction with Daunorubicin. Notably, normal cells exposed to an electric field did not show significant damage, indicating a selective effect on dividing cancer cells (U937). Moreover, the electric field affects the U937 cell line either alone or in combination with Daunorubicin. This effect may be due to increased membrane permeability.
CONCLUSIONS
Our findings suggest that the use of electric fields at intermediate frequencies and low intensities, either alone or in combination with Daunorubicin, has potential as a selective anti-cancer therapy for dividing cancer cells, particularly in the treatment of acute myeloid leukemia. Further research is needed to fully understand the underlying mechanisms and to optimize the use of this therapy.
Topics: Humans; U937 Cells; Blood Cells; Hematologic Neoplasms; Treatment Outcome; Daunorubicin
PubMed: 37700230
DOI: 10.1186/s12885-023-11339-7 -
PharmacoEconomics Jan 1992
Comparative Study
Topics: Cost-Benefit Analysis; Daunorubicin; Hospital Charges; Hospital Costs; Humans; Leukemia, Myeloid; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 10147103
DOI: 10.2165/00019053-199201010-00012 -
Cancer Chemotherapy and Pharmacology 1986
Clinical Trial Comparative Study Review
Topics: Animals; Antibiotics, Antineoplastic; Cardiomyopathies; Clinical Trials as Topic; Daunorubicin; Doxorubicin; Epirubicin; Female; Guinea Pigs; Heart; Humans; Idarubicin; Male; Menogaril; Mice; Nogalamycin; Rabbits; Rats
PubMed: 2948729
DOI: 10.1007/BF00273384 -
Lancet (London, England) Oct 1975
Topics: Adult; Daunorubicin; Female; Heart Arrest; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Time Factors
PubMed: 52088
DOI: 10.1016/s0140-6736(75)90814-4 -
Drugs Under Experimental and Clinical... 1986Analogue development is one of the most intensively pursued anticancer drugs research projects. The rationale in anthracycline analogue development followed by... (Clinical Trial)
Clinical Trial Review
Analogue development is one of the most intensively pursued anticancer drugs research projects. The rationale in anthracycline analogue development followed by Farmitalia Carlo Erba has been the selection of agents with improved therapeutic index with respect to the parent structures, different spectrum of activity, reduced toxicity to the myocardium and oral route of administration. The clinical development is based on Phase I, II and III studies. However, the best definition in terms of activity and toxicity of an anticancer agent is accomplished with Phase II clinical trials, especially if they are comparative in a randomized fashion with the parent compound. Esorubicin has just started Phase II clinical testing. Phase I studies have shown hints of activity in several malignant diseases. Idarubicin has already been shown to be an important antileukaemic agent in Phase II-III studies. Moreover this compound is the first oral anthracycline that has shown activity in breast cancer, lymphomas and leukaemias, together with potential for reduced cardiac toxicity. Epirubicin, which is now in Phase III clinical development, has been shown to possess a better therapeutic index than doxorubicin since it induces less acute toxicities (nausea and vomiting, mucositis, myelosuppression) and less cardiotoxicity than its parent compound, without loss of activity in responsive tumours.
Topics: Antibiotics, Antineoplastic; Bone Marrow; Clinical Trials as Topic; Daunorubicin; Doxorubicin; Drug Evaluation; Epirubicin; Heart; Humans; Idarubicin; Neoplasms
PubMed: 3525075
DOI: No ID Found -
The Journal of Antibiotics May 1977
Topics: Acetylation; Bacillus cereus; Biotransformation; Daunorubicin
PubMed: 407204
DOI: 10.7164/antibiotics.30.425 -
Journal of Medicinal Chemistry Nov 1980The synthesis of amino acid and dipeptide derivatives of daunorubicin (DNR) is described. The binding-affinity parameters for DNA of those derivatives were determined by...
The synthesis of amino acid and dipeptide derivatives of daunorubicin (DNR) is described. The binding-affinity parameters for DNA of those derivatives were determined by a spectral titration method. The affinity constants of the amino acid and dipeptide derivatives are, respectively, three and ten times lower than that of DNR. The susceptibility of those derivatives toward lysosomal peptidases was studied. It was found that the Leu and the Ala-Leu derivatives are the most rapidly hydrolyzed into DNR. It is concluded that Leu-DNR and Ala-Leu-DNR could act as prodrugs of DNR, which could be activated inside or in the close vicinity of tumor cells which display a high aminopeptidase activity.
Topics: Animals; Chemical Phenomena; Chemistry, Physical; DNA; Daunorubicin; Fishes; Hydrogen-Ion Concentration; Hydrolysis; In Vitro Techniques; Liver; Lysosomes; Rats
PubMed: 7452665
DOI: 10.1021/jm00185a003