Article ; Online: Evaluation of cytochrome P450-based drug metabolism in hemorrhagic shock rats that were transfused with native and an artificial red blood cell preparation, Hemoglobin-vesicles.
Drug metabolism and pharmacokinetics
2020 Volume 35, Issue 5, Page(s) 417–424
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 ... but not clinically significant effect on drug metabolism via CYPs in the liver due to decreased protein ...
| 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. |
|---|---|
| MeSH term(s) | Animals ; Caffeine/chemistry ; Caffeine/metabolism ; Chlorzoxazone/chemistry ; Chlorzoxazone/metabolism ; Cytochrome P-450 Enzyme System/chemistry ; Cytochrome P-450 Enzyme System/metabolism ; Drug Interactions ; Hemoglobins/chemistry ; Hemoglobins/metabolism ; Liposomes/chemistry ; Liposomes/metabolism ; Male ; Midazolam/chemistry ; Midazolam/metabolism ; Rats ; Rats, Sprague-Dawley ; Shock, Hemorrhagic/metabolism ; Tolbutamide/chemistry ; Tolbutamide/metabolism |
| Chemical Substances | Hemoglobins ; Liposomes ; Caffeine (3G6A5W338E) ; Cytochrome P-450 Enzyme System (9035-51-2) ; Tolbutamide (982XCM1FOI) ; Chlorzoxazone (H0DE420U8G) ; Midazolam (R60L0SM5BC) |
| Keywords | covid19 |
| Language | English |
| Publishing date | 2020-06-27 |
| Publishing country | England |
| Document type | Journal Article |
| ZDB-ID | 2095748-8 |
| ISSN | 1880-0920 ; 1347-4367 ; 0916-1139 |
| ISSN (online) | 1880-0920 |
| ISSN | 1347-4367 ; 0916-1139 |
| DOI | 10.1016/j.dmpk.2020.06.004 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
Full text online
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 3734: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.