毒理学相关资料,第五章内容参考文献25.pdfVIP

0022-3565/01/2972-509–515$3.00 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 297, No. 2 Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics 3298/897755 JPET 297:509–515, 2001 Printed in U.S.A. Primaquine-Induced Hemolytic Anemia: Formation and Hemotoxicity of the Arylhydroxylamine Metabolite 6-Methoxy- 8-hydroxylaminoquinoline LAURA J. C. BOLCHOZ, ROBERT A. BUDINSKY,1 DAVID C. MCMILLAN, and DAVID J. JOLLOW Department of Pharmacology, Medical University of South Carolina, Charleston, South Carolina Received September 6, 2000; accepted January 16, 2001 This paper is available online at ABSTRACT Primaquine is an important antimalarial agent because of its oquinoline (MAQ-NOH) by HPLC and mass spectral analyses. activity against exoerythrocytic forms of Plasmodium spp. As measured by decreased survival of 51Cr-labeled erythro- However, methemoglobinemia and hemolytic anemia are dose- cytes in rats, MAQ-NOH was hemolytic in vivo. Furthermore, in limiting side effects of primaquine therapy that limit its efficacy. vitro exposure of 51Cr-labeled erythrocytes to MAQ-NOH These hemotoxicities are thought to be mediated by metabo- caused a concentration-dependent decrease in erythrocyte lites; however, the identity of the toxic species has remained survival (EC50 of 350 M) when the exposed cells were returned unclear. Since N-hydroxy metabolites are known to mediate the to the circulation of isologous rats. MAQ-NOH also induced the hemotoxicity of several arylamines, the present