Abstract |
Hemoglobin-vesicles (Hb-V) are being developed as red blood cell (RBC) substitutes. In this study, we report on quantitative and qualitative alterations of hepatic cytochrome P450 (CYPs) and the pharmacokinetics of CYP-metabolizing drugs, with a focus on four CYP isoforms ( CYP1A2, CYP2C11, CYP2E1 and CYP3A2), after Hb-V resuscitation from a massive hemorrhage. The results of proteome analysis and western blot data indicate that resuscitation with both Hb-V and packed RBC (PRBC) resulted in a decrease in the protein levels of CYPs. Along with a decrease in the protein expression of CYPs, pharmacokinetic studies showed that the elimination of CYP-metabolizing drugs was prolonged in the Hb-V and PRBC resuscitation groups. It is also noteworthy that the CYP-metabolizing drugs in the Hb-V resuscitation group was retained for a longer period compared to the PRBC resuscitation group, and this is attributed to the CYP isoforms having a lower metabolic activity in the Hb-V resuscitation group than that for the PRBC resuscitation group. These findings suggest that resuscitation with Hb-V after a massive hemorrhage has a slight but not clinically significant effect on drug metabolism via CYPs in the liver due to decreased protein levels and the metabolic activity with respect to the CYPs.
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Authors | Masahiro Tokuno, Kazuaki Taguchi, Hiromi Sakai, Sumio Ohtsuki, Keishi Yamasaki, Masaki Otagiri |
Journal | Drug metabolism and pharmacokinetics
(Drug Metab Pharmacokinet)
Vol. 35
Issue 5
Pg. 417-424
(Oct 2020)
ISSN: 1880-0920 [Electronic] England |
PMID | 32792327
(Publication Type: Journal Article)
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Copyright | Copyright © 2020 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved. |
Chemical References |
- Hemoglobins
- Liposomes
- Caffeine
- Cytochrome P-450 Enzyme System
- Tolbutamide
- Chlorzoxazone
- Midazolam
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Topics |
- Animals
- Caffeine
(chemistry, metabolism)
- Chlorzoxazone
(chemistry, metabolism)
- Cytochrome P-450 Enzyme System
(chemistry, metabolism)
- Drug Interactions
- Hemoglobins
(chemistry, metabolism)
- Liposomes
(chemistry, metabolism)
- Male
- Midazolam
(chemistry, metabolism)
- Rats
- Rats, Sprague-Dawley
- Shock, Hemorrhagic
(metabolism)
- Tolbutamide
(chemistry, metabolism)
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