RT Journal Article
SR Electronic
T1 Repeated Injection of High Doses of Hemoglobin-Encapsulated Liposomes (Hemoglobin Vesicles) Induces Accelerated Blood Clearance in a Hemorrhagic Shock Rat Model
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 484
OP 489
DO 10.1124/dmd.110.036913
VO 39
IS 3
A1 Taguchi, Kazuaki
A1 Iwao, Yasunori
A1 Watanabe, Hiroshi
A1 Kadowaki, Daisuke
A1 Sakai, Hiromi
A1 Kobayashi, Koichi
A1 Horinouchi, Hirohisa
A1 Maruyama, Toru
A1 Otagiri, Masaki
YR 2011
UL http://dmd.aspetjournals.org/content/39/3/484.abstract
AB The hemoglobin vesicle (HbV) is an artificial oxygen carrier in which a concentrated hemoglobin solution is encapsulated in a liposome. To apply liposome preparations in clinics, it is important to consider the accelerated blood clearance phenomenon (ABC phenomenon), which involves a loss in the long-circulation half-life after being administered repeatedly to the same animals. The objective of this study was to determine whether the ABC phenomenon is induced by repeated injection of HbV under conditions of hemorrhagic shock. We created a rat model of hemorrhagic shock and performed a pharmacokinetic study using 125I-HbV, in which the Hb inside of HbV was labeled with 125I. At 4 and 7 days after resuscitation from hemorrhagic shock by nonlabeled HbV (1400 mg Hb/kg), the second dose of 125I-HbV (1400 mg Hb/kg) was rapidly cleared from the circulation compared with normal rats. Of interest, IgM against HbV was produced at 4 days after the first injection of HbV, but decreased at 7 days. In addition, phagocyte activity was increased at both 4 and 7 days after the first injection of HbV. These results suggest that repeated injections of HbV at a dose of 1400 mg Hb/kg induce the ABC phenomenon under conditions of hemorrhagic shock, which is strongly related to both the production of anti-HbV IgM and enhanced phagocyte activity. We thus conclude that it might be necessary to considerer the ABC phenomenon in the dose regimen of HbV treatment in clinical settings.