Pharmacokinetics of bleomycin in man

Alberts, David S.; Chen, Hsiao Sheng G.; Woolfenden, James M.; Moon, Thomas E.; Chang, Su-Youne; Hall, Jack N.; Himmelstein, Kenneth J.; Gross, Joseph F.; Salmon, Sydney E.

doi:10.1007/bf00254417

Cited by 11 publications

(5 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…20, 21 However, the therapeutic efficacy of this relatively insoluble small-molecule drug is limited by its low bioavailability and short-plasma half-life, necessitating frequent dosing. 22 In addition, the often life-threatening side effects (cardiotoxicity, 23 bone marrow suppression, 24, 25 infertility, 26 etc.) that accompany the use of doxorubicin, including latent development of leukemia after prolonged treatment, 27 deem this an undesirable chemotherapeutic agent.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and in vitro activity of ROMP-based polymer nanoparticles

et al. 2009

View full text Add to dashboard Cite

A new type of polymer nanoparticle (PNP) containing a high density of covalently linked doxorubicin, attached via a non-cleavable amine linkage (amine-linked Dox-PNP) was prepared. Together with a previously reported cleavable carbamate-linked Dox-PNP, this new amine-linked Dox-PNP was subsequently evaluated against free doxorubicin for its cytotoxicity and inhibitory effects on SKNSH wild-type and SKrDOX6 doxorubicin-resistant human neuroblastoma cell lines. Analogous cholesterol-containing PNPs (Chol-PNPs) and indomethacin-containing PNPs (IND-PNPs) were also synthesized and used as the non-cytotoxic controls. While neither cell line was affected by Chol-PNPs or IND-PNPs, SKrDOX6 doxorubicin-resistant cells exhibited similar cytotoxic responses to free doxorubicin and both amine- and carbamate-linked Dox-PNPs, suggesting that doxorubicin or the doxorubicin-containing polymer must be the active agent in the latter case. SKNSH wild-type cells also responded to both Dox-PNPs, albeit at a higher apparent concentration than free doxorubicin alone. The growth of SKNSH wild-type cells was significantly inhibited upon incubation with carbamate-linked Dox-PNPs, as with free doxorubicin, over a 7-day period. In comparison to free doxorubicin, carbamate-linked Dox-PNPs produced a longer (72-h) period of initial inhibition in SKrDOX6 doxorubicin-resistant cells.

show abstract

Section: Resultsmentioning

confidence: 99%

Synthesis and in vitro activity of ROMP-based polymer nanoparticles

et al. 2009

View full text Add to dashboard Cite

show abstract

“…[45][46][47][48] Knowing that the efficacy of agonists is dependent on the levels of receptor expressed in a tissue, we observed, as expected, that most of the compounds with a DpIC 50 (H-L) value below or equal to 0.4 for a 2A -AR behaved as partial agonists in our [ 35 S]GTPgS binding assay performed in Chinese hamster ovary (CHO) cells expressing high levels of the human recombinant receptor but behaved as antagonists of a 2A -AR in paced isolated rat vas deferens expressing physiologically relevant levels of the receptor. [49][50][51] The absence of mydriase in the Irwin test reflected an additional argument in favor of a a 2A -AR antagonist behavior. We therefore classified compounds displaying a DpIC 50 (H-L) value below or equal to 0.4 as antagonist of a 2A -AR.…”

mentioning

confidence: 99%

Discovery of Selective Alpha_2C Adrenergic Receptor Agonists

et al. 2012

View full text Add to dashboard Cite

Something to ease the pain: Chemical modification of a 2‐amino‐oxazoline scaffold led to the identification of α2C adrenergic receptor (AR) agonists. These ligands were characterized by a dual α2C‐AR agonist/α2A‐AR antagonist profile. Structure–activity relationships were studied, and screening in anesthetized rats demonstrated a superior margin of safety for this class of compounds with respect to cardiovascular effects compared with nonselective α2‐AR agonists.

show abstract

“…Pilot studies go back to the mid-1970s, when Walter Wolf at the University of Southern California proposed using Pt-195m-labeled cisplatin, [15][16][17] and a group at the University of Arizona used Co-57 bleomycin (although not specifically to evaluate targeting). 18,19 The related approach of using the same agent at low dose for diagnostic imaging and at high dose for therapy is also not new. The best exemplar is probably I-131 sodium iodide in differentiated thyroid carcinoma (or, alternatively, I-123 for diagnosis and I-131 for therapy).…”

Section: Extension Of Therapy Operating Characteristic Methodology Tomentioning

confidence: 99%

Therapy operating characteristic curves: tools for precision chemotherapy

et al. 2016

View full text Add to dashboard Cite

The therapy operating characteristic (TOC) curve, developed in the context of radiation therapy, is a plot of the probability of tumor control versus the probability of normal-tissue complications as the overall radiation dose level is varied, e.g., by varying the beam current in external-beam radiotherapy or the total injected activity in radionuclide therapy. This paper shows how TOC can be applied to chemotherapy with the administered drug dosage as the variable. The area under a TOC curve (AUTOC) can be used as a figure of merit for therapeutic efficacy, analogous to the area under an ROC curve (AUROC), which is a figure of merit for diagnostic efficacy. In radiation therapy, AUTOC can be computed for a single patient by using image data along with radiobiological models for tumor response and adverse side effects. The mathematical analogy between response of observers to images and the response of tumors to distributions of a chemotherapy drug is exploited to obtain linear discriminant functions from which AUTOC can be calculated. Methods for using mathematical models of drug delivery and tumor response with imaging data to estimate patient-specific parameters that are needed for calculation of AUTOC are outlined. The implications of this viewpoint for clinical trials are discussed.

show abstract

Pharmacokinetics of bleomycin in man

Cited by 11 publications

References 7 publications

Synthesis and in vitro activity of ROMP-based polymer nanoparticles

Synthesis and in vitro activity of ROMP-based polymer nanoparticles

Discovery of Selective Alpha_2C Adrenergic Receptor Agonists

Therapy operating characteristic curves: tools for precision chemotherapy

Contact Info

Product

Resources

About

Pharmacokinetics of bleomycin in man

Cited by 11 publications

References 7 publications

Synthesis and in vitro activity of ROMP-based polymer nanoparticles

Synthesis and in vitro activity of ROMP-based polymer nanoparticles

Discovery of Selective Alpha2C Adrenergic Receptor Agonists

Therapy operating characteristic curves: tools for precision chemotherapy

Contact Info

Product

Resources

About

Discovery of Selective Alpha_2C Adrenergic Receptor Agonists