Assessing cytochrome P450-based drug-drug interactions with hemoglobin-vesicles, an artificial red blood cell preparation, in healthy rats

Masahiro Tokuno, Kazuaki Taguchi, Hiromi Sakai, Sumio Ohtsuki, Keishi Yamasaki, Masaki Otagiri

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Hemoglobin-vesicles (Hb-V), hemoglobin encapsulated within a liposome, were developed as an artificial red blood cell (RBC). When Hb-V becomes clinically available in the future, patients would presumably be co-administered with one or more drugs. Since drug-drug interactions can cause serious adverse effects and impede overall curative effects, evidence regarding the risk associated with drug-drug interactions between Hb-V and such simultaneously administered drugs is needed. Therefore, we report on cytochrome P450 (CYP)-based drug interactions with Hb-V in healthy rats. At 1 day after the saline, Hb-V or packed RBC (PRBC) administration, the blood retention of CYP-metabolizing drugs (caffeine, chlorzoxazone, tolbutamide and midazolam) were moderately prolonged in the case of the Hb-V group, but not the PRBC group, compared to saline group. The results of a proteome analysis revealed that the Hb-V administration had only negligible effects on the protein expression of CYPs in the liver. Hb-V administration, however, clearly suppressed the CYP metabolic activity of the four target CYP isoforms compared with the saline and PRBC group. However, these alterations were nearly recovered at 7 day after the Hb-V administration. Taken together, these results suggest that the administration of Hb-V slightly and transiently affects the CYP-based metabolism of the above drugs.

Original languageEnglish
JournalDrug Metabolism And Pharmacokinetics
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • Artificial blood
  • Cytochrome P450
  • Drug-drug interaction
  • Hemoglobin
  • Proteomics
  • Red blood cell

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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