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• W2227563131 abstract "2093 Background: The clinical utility of doxorubicin is limited by toxicity that may preclude adequate dosing and diminished its therapeutical effect on relapse, or lead to drug resistance. Caelyx, a doxorubicin formulation of polyethylene glycol-coated liposomes, has demonstrated activity against solid tumors. For this new form of doxorubicin, a superior pharmacokinetic profile over that of free doxorubicin is postulated. It is also theorized that there is a minimal drug-leakage of these long circulating particles, due to an exceeding of the water solubility of doxorubicin in the liposomes. It was the aim of this study, to analyze the plasma levels as well as the cellular uptake of encapsulated and free doxorubicin. Methods: Caelyx was administered i.v. at doses of 30, 40, 50, and 60 mg/m2 within one hour, once every 28 days, for as long as patients respond to and tolerate treatment. To answer the question of a possible accumulation of Caelyx, plasma and urine samples of 30 patients receiving 51 courses, were analyzed for PK calculations. In addition, cellular uptake of doxorubicin was analyzed in single intra-individual comparisons. Results: There is no evidence for an accumulation of the free doxorubicin in plasma up to a dose of 50 mg/m2 Caelyx every four weeks. The mean terminal half life for Caelyx was calculated as 3 days, MRT about 5 days, the Vss 1.5 l, CL was determined to be less than 1 ml/min. There was no detectable renal excretion of the intact liposomes. The calculated PK parameters for the released doxorubicin gave evidence for an increased AUC and MRT, and a decreased Cmax and CL, in comparison to earlier published PK parameters of conventionally administered free doxorubicin. Cellular uptake of doxorubicin increased after application of Caelyx, compared to the intra-individual uptake of the equivalent conventional dose of doxorubicin. Conclusions: In addition to the indirect tumor targeting using the long circulating pegylated liposomes, the slow release of doxorubicin enables the treatment of potential micro metastases, enables the practical use of the anti-angiogenic potential of doxorubicin and furthermore offers an option in the management of leukemia. No significant financial relationships to disclose." @default.
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• W2227563131 date "2005-06-01" @default.
• W2227563131 modified "2023-09-25" @default.
• W2227563131 title "Pharmacokinetics (PK) of the liposomal encapsulated fraction as well as released doxorubicin after intravenous infusion of liposomal doxorubicin" @default.
• W2227563131 doi "https://doi.org/10.1200/jco.2005.23.16_suppl.2093" @default.
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