Possible Isozyme-specific Effects of Experimental Malaria Infection with Plasmodium berghei on Cytochrome P450 Activity in Rat Liver Microsomes-Reference-Cited by-同舟云学术

Possible Isozyme-specific Effects of Experimental Malaria Infection with Plasmodium berghei on Cytochrome P450 Activity in Rat Liver Microsomes

Published:1994-05 Issue:5 Volume:46 Page:352-355
ISSN:2042-7158
Container-title:Journal of Pharmacy and Pharmacology
language:en
Short-container-title:

Author:

Glazier A P¹,Kokwaro G O¹,Edwards G²

Affiliation:

1. Department of Pharmacology and Therapeutics, University of Liverpool, Ashton Street, Liverpool L69 3BX

2. Division of Biomedical Science, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK

Abstract

Abstract We have investigated the effect of experimental malaria infection on rat cytochrome P450-mediated drug metabolism using ethoxyresorufin and metoprolol as probe compounds. Malaria infection caused a significant reduction in total intrinsic clearance of ethoxyresorufin in both low and high parasitaemia malaria compared with control (control 18·7 ± 7·2; low parasitaemia 10·5 ± 4·1; high parasitaemia 4·3 ± 1·4 mL min−1). However, clearance of metoprolol was unchanged in malaria infection compared with control (control 2·7±1·2; malaria 4·0±1·7 mL min−1). The change in clearance of ethoxyresorufin was the result of a decrease in Vmax, with no apparent change in Km. There was no change in either Vmax or Km of metoprolol. These results indicate a possible isozyme-selective effect of experimental malaria.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

Link

http://academic.oup.com/jpp/article-pdf/46/5/352/36993216/j.2042-7158.1994.tb03811.x.pdf

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