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• W2170484811 abstract "Abstract N 4-Hexadecyl-1-β-d-arabinofuranosylcytosine (NHAC) is a new lipophilic derivative of 1-β-d-arabino-furanosylcytosine (ara-C) with strong antitumour activity. The interactions of NHAC incorporated into small unilamellar liposomes of different compositions with blood components were evaluated. In comparison with ara-C, NHAC is highly protected against deamination to inactive arabinofurano-syluracil (ara-U) in human plasma, resulting in only 2% conversion into ara-U after 4 h incubation at 37°C, whereas from ara-C more than 80% was deaminated. In in-vitro incubations with human blood, it was found that NHAC was transferred from the liposomes at about 47% efficiency to plasma proteins, particularly to albumin and to the high and low density lipoproteins. The remaining part of NHAC was bound to erythrocytes (50%) and to leucocytes (3%). The addition of poly(ethylene) glycol-modified phospholipids to the liposomes (PEG liposomes), which were composed of soy phosphatidylcholine and cholesterol (plain liposomes), did not significantly prevent the fast transfer of NHAC from the liposomes to the blood components. Pharmacokinetic studies in mice revealed that NHAC had biphasic kinetics in blood with a t 1/2α of 16 min and a 1/2β of 3·8 h when the drug was formulated in plain liposomes and a t 1/2α of 15 min and a t 1/2β of 9·67 h in PEG liposomes, respectively. NHAC was predominantly distributed in the liver with 29% of the injected dose found after 30 min. However, no accumulation occurred in the liver and NHAC was eliminated with biphasic kinetics resulting in a t 1/2α of 53 min and a t 1/2β of 11·8 h. In spleen, kidney and bone marrow the levels of NHAC remained low. In summary, NHAC is highly resistant against deamination and rapidly transferred from the liposomes to the blood components, independently of the liposome compositions tested." @default.
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• W2170484811 date "1995-04-01" @default.
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• W2170484811 title "Pharmacokinetic Properties and Interactions with Blood Components of N4-Hexadecyl-1-β-d-arabinofuranosylcytosine (NHAC) Incorporated into Liposomes" @default.
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• W2170484811 doi "https://doi.org/10.1111/j.2042-7158.1995.tb05796.x" @default.
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