Document Detail


Antimalarial interaction of quinine and quinidine with clarithromycin.
MedLine Citation:
PMID:  23137860     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
SUMMARY Quinine (QN) and quinidine (QND) have been commonly used as effective and affordable antimalarials for over many years. Quinine primarily is used for severe malaria treatment. However, plasmodia resistance to these drugs and poor patient compliance limits their administration to the patients. The declining sensitivity of the parasite to the drugs can thus be dealt with by combining with a suitable partner drug. In the present study QN/QND was assessed in combination with clarithromycin (CLTR), an antibiotic of the macrolide family. In vitro interactions of these drugs with CLTR against Plasmodium falciparum (P. falciparum) have shown a synergistic response with mean sum fractional inhibitory concentrations (ΣFICs) of ⩽1 (0·85 ± 0·11 for QN + CLTR and 0·64 ± 0·09 for QND + CLTR) for all the tested combination ratios. Analysis of this combination of QN/QND with CLTR in mouse model against Plasmodium yoelii nigeriensis multi-drug resistant (P. yoelii nigeriensis MDR) showed that a dose of 200 mg/kg/day for 4 days of QN or QND produces 100% curative effect with 200 mg/kg/day for 7 days and 150 mg/kg/day for 7 days CLTR respectively, while the same dose of individual drugs could produce only up to a maximum 20% cure. It is postulated that CLTR, a CYP3A4 inhibitor, might have caused reduced CYP3A4 activity leading to increased plasma level of the QN/QND to produce enhanced antimalarial activity. Further, parasite apicoplast disruption by CLTR synergies the antimalarial action of QN and QND.
Authors:
Swaroop Kumar Pandey; Hemlata Dwivedi; Sarika Singh; Waseem Ahmad Siddiqui; Renu Tripathi
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-9
Journal Detail:
Title:  Parasitology     Volume:  -     ISSN:  1469-8161     ISO Abbreviation:  Parasitology     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0401121     Medline TA:  Parasitology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  1-8     Citation Subset:  -    
Affiliation:
Division of Parasitology, CSIR-CDRI, Lucknow, India-226001.
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