PMID- 9434284
OWN - NLM
STAT- MEDLINE
DCOM- 19980219
LR  - 20190818
IS  - 0724-8741 (Print)
IS  - 0724-8741 (Linking)
VI  - 14
IP  - 11
DP  - 1997 Nov
TI  - Pharmacokinetic and pharmacological profiles of free and liposomal recombinant 
      human erythropoietin after intravenous and subcutaneous administrations in rats.
PG  - 1621-8
AB  - 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 micron 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 pharmacokinetics 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.
FAU - Moriya, H
AU  - Moriya H
AD  - Department of Pharmaceutics, Hoshi University, Tokyo, Japan.
FAU - Maitani, Y
AU  - Maitani Y
FAU - Shimoda, N
AU  - Shimoda N
FAU - Takayama, K
AU  - Takayama K
FAU - Nagai, T
AU  - Nagai T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Pharm Res
JT  - Pharmaceutical research
JID - 8406521
RN  - 0 (Liposomes)
RN  - 11096-26-7 (Erythropoietin)
SB  - IM
MH  - Animals
MH  - Erythropoietin/blood/*pharmacokinetics/*pharmacology
MH  - Humans
MH  - Injections, Intravenous
MH  - Injections, Subcutaneous
MH  - Liposomes/*pharmacokinetics/*pharmacology
MH  - Lymph/metabolism
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - Reticulocytes/metabolism
EDAT- 1998/01/22 00:00
MHDA- 1998/01/22 00:01
CRDT- 1998/01/22 00:00
PHST- 1998/01/22 00:00 [pubmed]
PHST- 1998/01/22 00:01 [medline]
PHST- 1998/01/22 00:00 [entrez]
AID - 10.1023/a:1012142704924 [doi]
PST - ppublish
SO  - Pharm Res. 1997 Nov;14(11):1621-8. doi: 10.1023/a:1012142704924.