caa a22 4500 477128424 CHVBK 20180405111656.0 cr unu---uuuuu 170330e19971101xx s 000 0 eng 10.1023/A:1012142704924 doi (NATIONALLICENCE)springer-10.1023/A:1012142704924 Pharmacokinetic and Pharmacological Profiles of Free and Liposomal Recombinant Human Erythropoietin After Intravenous and Subcutaneous Administrations in Rats [Elektronische Daten] [Hidetaka Moriya, Yoshie Maitani, Naoto Shimoda, Kozo Takayama, Tsuneji Nagai] Purpose. Recombinant human erythropoietin (Epo) is used frequently through intravenous (i.v.) and subcutaneous (s.c.) administration for the clinical treatment of the last stage of renal anemia. We encapsulated Epo in liposomes to develop an alternative administration route. The purpose of our study was to evaluate the pharmacokinetics and the pharmacological effects of liposomal Epo in comparison with the Epo after i.v. and s.c. administration to rats. Methods. Epo was encapsulated in liposomes composed of dipalmitoylphosphatidylcholine (DPPC) and soybean-derived sterol mixture (SS) prepared by the reversed-phase evaporation vesicle method. After filtration through a 0.1 μm polycarbonate membrane, liposomes were gel filtered (Epo/liposomes). Results. Epo/liposomes showed higher pharmacological activity than Epo/liposomes before gel filtration after i.v. administration to rats. Non-encapsulated Epo lost its activity, whereas encapsulated Epo in liposomes retained it. The pharmacological effects of Epo/liposomes were greater than those of Epo after i.v. administration. Epo/liposomes afforded 3−9 times higher AUC, lower clearance and lower steady-state volume of distribution than Epo after both i.v. and s.c. administrations. Epo/liposomes had an improved pharmacokinetic profile compared with Epo. S.c. administration of Epo/liposomes at 7 h may penetrate primarily (40% of dose) through the blood as a liposome and partly (7% of dose) in lymph. Conclusions. Epo/liposomes may reduce the frequency of injections required for a certain reticulocyte effect in comparison to Epo. The lower clearance of Epo/liposomes may increase the plasma concentrations of Epo, which increases the efficacy. Plenum Publishing Corporation, 1997 recombinant human erythropoietin nationallicence liposome nationallicence intravenous administration nationallicence subcutaneous administration nationallicence pharmacokinetics nationallicence pharmacological effect nationallicence Moriya Hidetaka Department of Pharmaceutics, Hoshi University, 2-4-41 Ebara, Shina-gawa-ku, 142, Tokyo, Japan aut Maitani Yoshie Department of Pharmaceutics, Hoshi University, 2-4-41 Ebara, Shina-gawa-ku, 142, Tokyo, Japan aut Shimoda Naoto Preclinical Development Division, Chugai Pharmaceutical Co., Ltd., 3-41-8 Takada, Toshima-ku, 171, Tokyo, Japan aut Takayama Kozo Department of Pharmaceutics, Hoshi University, 2-4-41 Ebara, Shina-gawa-ku, 142, Tokyo, Japan aut Nagai Tsuneji Department of Pharmaceutics, Hoshi University, 2-4-41 Ebara, Shina-gawa-ku, 142, Tokyo, Japan aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/11(1997-11-01), 1621-1628 0724-8741 14:11<1621 1997 14 11095 https://doi.org/10.1023/A:1012142704924 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012142704924 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Moriya Hidetaka Department of Pharmaceutics, Hoshi University, 2-4-41 Ebara, Shina-gawa-ku, 142, Tokyo, Japan aut NATIONALLICENCE 700 1- Maitani Yoshie Department of Pharmaceutics, Hoshi University, 2-4-41 Ebara, Shina-gawa-ku, 142, Tokyo, Japan aut NATIONALLICENCE 700 1- Shimoda Naoto Preclinical Development Division, Chugai Pharmaceutical Co., Ltd., 3-41-8 Takada, Toshima-ku, 171, Tokyo, Japan aut NATIONALLICENCE 700 1- Takayama Kozo Department of Pharmaceutics, Hoshi University, 2-4-41 Ebara, Shina-gawa-ku, 142, Tokyo, Japan aut NATIONALLICENCE 700 1- Nagai Tsuneji Department of Pharmaceutics, Hoshi University, 2-4-41 Ebara, Shina-gawa-ku, 142, Tokyo, Japan aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/11(1997-11-01), 1621-1628 0724-8741 14:11<1621 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer