Pharmacokinetic and imaging studies in patients receiving a formulation of liposome-associated adriamycin
Autor: | I. Fromer, Rivka Cohen, R. Chisin, Aaron Sulkes, Alberto Gabizon, Shimon Amselem, Dorit Goren, Tamar Peretz, Yechezkel Barenholz, S. Druckmann |
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Rok vydání: | 1991 |
Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Metabolic Clearance Rate Phases of clinical research Spleen Dosage form chemistry.chemical_compound Pharmacokinetics Neoplasms Internal medicine Phosphatidylcholine medicine Humans Doxorubicin Radionuclide Imaging Aged Liposome business.industry Indium Radioisotopes Middle Aged Endocrinology medicine.anatomical_structure Liver Oncology chemistry Liposomes Female Bone marrow business Research Article medicine.drug |
Zdroj: | British Journal of Cancer |
ISSN: | 1532-1827 0007-0920 |
Popis: | Pharmacokinetic and imaging studies in 19 patients receiving liposome-entrapped adriamycin (L-ADM) were carried out within the framework of a Phase I clinical trial (Gabizon et al., 1989a). The formulation of L-ADM tested consisted of 0.2 microM-extruded multilamellar vesicles composed of egg phosphatidylcholine, egg-derived phosphatidyl-glycerol (PG), cholesterol, and ADM intercalated in the fluid lipid bilayer. Plasma clearance of total drug extracted from the plasma after L-ADM infusion followed a biexponential curve with a pattern similar to that reported for free ADM. The plasma concentration of drug circulating in liposome-associated from was also measured in a subgroup of seven patients. Liposome-associated drug was found to be rapidly cleared from plasma. Its ratio to non-liposome-associated drug appeared to correlate with liver reserve, with highest ratios in patients with normal liver function. Liposome clearance, as measured by the plasma concentration of PG in three patients was slower than the clearance of liposome-associated ADM, suggesting that liposomes lose part of their drug payload during circulation. To learn about the liposome organ distribution, imaging studies were carried out with 111Indium-deferoxamine labelled liposomes of the same composition. Liposomes were cleared predominantly by liver and spleen and to a lesser extent by bone marrow in seven out of nine patients. In two patients with active hepatitis and severe liver dysfunction, there was minimal liver uptake and increased spleen and bone marrow uptake. Except for one hepatoma patient, intrahepatic and extrahepatic tumours were not imaged by liposomes, suggesting that liposome uptake is restricted to cells of the reticulo-endothelial system (RES).(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 |
Databáze: | OpenAIRE |
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