HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Watt, G. Articles by Webster, H. K. Search for Related Content PubMed PubMed Citation Articles by Watt, G. Articles by Webster, H. K.

Amplification of Quinine Cardiac Effects by the Resistance-Reversing Agent Prochlorperazine in Falciparum Malaria

The use of reversing agents to overcome drug resistance is a potential new treatment strategy for both malaria and cancer. Laboratory studies have raised questions about the safety of this therapeutic approach, but data in humans are lacking. We therefore assessed the toxic potential of reversing agent therapy in Thai patients receiving quinine (17 mg/kg given over 4.5 hr) for falciparum malaria by serial measurements of the QT_c interval, an electrocardiographic (ECG) marker of the effect of quinine. Six patients were randomly assigned to receive intravenous quinine alone while another six received one intramuscular injection of 12.5 mg of the reversing agent prochlorperazine (PC; compazine®, stemetil®) 2.5 hr after the quinine infusion had begun. Compared with baseline values at 2.5 hr, there was prolongation of the QT_c interval 30, 60, 90, and 120 min after PC was injected (P < 0.05) but no further lengthening with quinine alone (P > 0.2). Prochlorperazine alone did not lengthen the QT_c interval in six healthy volunteers. Neither total nor free quinine plasma levels increased after PC was injected, suggesting that ECG changes may have been due to PC-induced intracellular accumulation of quinine. Although only minor quinine ECG effects were amplified by the reversing agent PC in this study, resistance-reversing therapy could potentiate more serious drug effects. The possibility that more serious toxic effects could be produced by this therapeutic approach should be investigated further.