Pharmacokinetics of CPX-351 (Cytarabine/Daunorubicin HCl) Liposome injection in the mouse

Bayne, W.F.; Mayer, Lawrence D.; Swenson, Christine E.

doi:10.1002/jps.21620

Cited by 40 publications

(21 citation statements)

References 8 publications

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“…Because of the promising outcomes from the Phase I clinical trial, CPX-1 has advanced into a Phase II clinical trial in patients with colorectal cancer. Similarly, maintenance of the synergistic drug ratios in circulation has been demonstrated for CPX-351 and CPX-571, and the therapeutic efficacies of these two liposome drug cocktails were also superior to the saline-based cocktails [104,105]. Tardi In addition to the studies by Mayer and co-workers, development of anti-cancer liposome drug cocktails has been attempted by us and other research groups.…”

Section: Combinations Of Conventional Chemotherapeuticsmentioning

confidence: 90%

“…These two important concepts have been elegantly demonstrated through a series of studies by Mayer and co-workers, culminating in various anti-cancer liposomal drug cocktails in different phases of development. These liposome cocktails include CPX-1 (liposomal irinotecan:floxuridine in 1:1 molar ratio [100][101][102][103]), CPX-351 (liposomal cytarabine:daunorubicin in 5:1 molar ratio [104,105]) and CPX-571 (liposomal irinotecan:cisplatin in 7:1 molar ratio, see Table 2). …”

Section: Combinations Of Conventional Chemotherapeuticsmentioning

confidence: 99%

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Lipid-Based Nanoparticulate Systems for the Delivery of Anti-Cancer Drug Cocktails: Implications on Pharmacokinetics and Drug Toxicities

Chiu¹,

Wong²,

Ling³

et al. 2009

CDM

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The use of drug cocktails has become a widely adopted strategy in clinical cancer therapy. Cytotoxic drug cocktails are often administered based on maximum tolerated dose (MTD) of each agent, with the belief of achieving maximum cell kill through tolerable toxicity level. Yet, MTD administration may not have fully captured the therapeutic synergism that exists among the individual agents in the drug cocktail, as the response to a cocktail regimen, that is, whether the effect is synergistic or not, could be highly sensitive to the concentration ratios of the individual drugs at the site of action. It is important to realize that the inherently different pharmacokinetic profiles of the individual agents could have significant influence on the response to an anti-cancer drug cocktail by dictating the amount of the individual agents reaching the tumor site and therefore the concentration ratios. Furthermore, the individual agents may have unfavorable pharmacokinetic interactions that add to the difficulty in determining the therapeutic and/or toxicological effects of the drug cocktail. In this review, we will focus on how lipid-based nanoparticulate systems could address the above issues associated with anti-cancer drug cocktails. Specifically, we will highlight the use of liposome systems as the means to control and coordinate the delivery of various anti-cancer drug cocktails, encompassing conventional chemotherapeutics, chemosensitizing agents and molecularly targeted agents.

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Section: Combinations Of Conventional Chemotherapeuticsmentioning

confidence: 90%

Section: Combinations Of Conventional Chemotherapeuticsmentioning

confidence: 99%

Lipid-Based Nanoparticulate Systems for the Delivery of Anti-Cancer Drug Cocktails: Implications on Pharmacokinetics and Drug Toxicities

Chiu¹,

Wong²,

Ling³

et al. 2009

CDM

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show abstract

“…Liposomal coencapsulation of fludarabine/mitoxantrone benefits not only from sustained drug release, but also from maintaining a fixed concentration of the released components over a 72-h period [Zhao et al, 2007]. Similarly, liposomal araC/daunorubicin has improved drug-release properties [Feldman et al, 2007;Bayne et al, 2009]. In conclusion, chemotherapeutics such as NAs encapsulated in liposomes are protected from degradation by plasma enzymes and might slowly be released in time, thereby maintaining their therapeutic concentration.…”

Section: Liposomal Encapsulationmentioning

confidence: 96%

Metabolic limitations of the use of nucleoside analogs in cancer therapy may be overcome by application of nanoparticles as drug carriers: A review

Hajdo

Szulc

Klajnert

et al. 2010

Drug Development Research

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Purine and pyrimidine nucleoside analogs (NAs) are antimetabolites commonly used in cancer therapy. Administered as prodrugs, NAs permeate the mambrane using specialized transporters. Following phosphorylation, they interfere with multiple cellular pocessess inducing cytotoxicity. Toxic effects of NAs are dependent on metabolic conversion from a prodrug into the active form. For instance, an exceptionally high activity of deoxycytidine kinase (dCK) in lymphocytes is correlated with a good therapeutic effect of fludarabine in leukemic cells. On the other hand, several studies have shown that nucleoside-transporter (NT)-deficientcells are highly resistant to NAs. Attempts to overcome the metabolic limitations of chemotherapeutics would result in the use of lower drug doses for effective therapy, reduce side effects, and ensure the independence of drug resistance mechanisms. To meet this need, several nanoparticles have been designed to deliver efficently NAs directly to cancer cells. Such vehicles include liposomes, albumins, and dendritic and linear polymers. Therapeutic agents encapsulated or conjugated to nanoparticles have improved pharmacokinetics, solubility, and stability. These factors improve the efficacy of commonly used drugs. Moreover, modification of nanoparticles with targeting molecules such as sugar moieties or folic acid ensures more specific delivery without affecting healthy tissues. Drug Dev Res 71:383-394, 2010.

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“…These liposomes are then incubated with daunorubicin to achieve dual-drug encapsulation. 59 CPX-351 will be described in greater detail in the liposome section of this article. Currently liposomes are the only nanoparticle-based combinatorial drug delivery platform that has entered clinical trials.…”

Section: Nanoparticles As Multifunctional Drug Delivery Systemsmentioning

confidence: 99%

Recent Developments in Active Tumor Targeted Multifunctional Nanoparticles for Combination Chemotherapy in Cancer Treatment and Imaging

Glasgow¹,

Mb²

2015

j biomed nanotechnol

110

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Nanotechnology and combination therapy are two major fields that show great promise in the treatment of cancer. The delivery of drugs via nanoparticles helps to improve drug’s therapeutic effectiveness while reducing adverse side effects associated with high dosage by improving their pharmacokinetics. Taking advantage of molecular markers over-expressing on tumor tissues compared to normal cells, an “active” molecular marker targeted approach would be beneficial for cancer therapy. These actively targeted nanoparticles would increase drug concentration at the tumor site, improving efficacy while further reducing chemo-resistance. The multidisciplinary approach may help to improve the overall efficacy in cancer therapy. This review article summarizes recent developments of targeted multifunctional nanoparticles in the delivery of various drugs for a combinational chemotherapy approach to cancer treatment and imaging.

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Pharmacokinetics of CPX-351 (Cytarabine/Daunorubicin HCl) Liposome injection in the mouse

Cited by 40 publications

References 8 publications

Lipid-Based Nanoparticulate Systems for the Delivery of Anti-Cancer Drug Cocktails: Implications on Pharmacokinetics and Drug Toxicities

Lipid-Based Nanoparticulate Systems for the Delivery of Anti-Cancer Drug Cocktails: Implications on Pharmacokinetics and Drug Toxicities

Metabolic limitations of the use of nucleoside analogs in cancer therapy may be overcome by application of nanoparticles as drug carriers: A review

Recent Developments in Active Tumor Targeted Multifunctional Nanoparticles for Combination Chemotherapy in Cancer Treatment and Imaging

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