Antimalarial-Antibiotic Combination for Malaria: Evaluation of the Potential Toxicity and Safety of the Combinations of Amodiaquine-Ciprofloxacin and Amodiaquine-Rifampicin

Abstract

The combinations of antibiotics with standard anti-malarial drugs have been documented as potentially valuable chemotherapeutic options for the management of drug-resistant malaria infections. However, the potential adverse effects and/ or toxic manifestation of the combinations remain to be addressed. This study was designed to investigate the probable toxicological effect of the combination of amodiaquine with rifampicin or ciprofloxacin. Forty-two Swiss mice with average weight of 24 g were divided into six groups. They were treated orally with Amodiaquine (10 mg/kg), Ciprofloxacin (160 mg/kg), Rifampicin (15 mg/kg), Amodiaquine plus Rifampicin or Ciprofloxacin and 0.2 mL saline solution respectively. Biochemical and hematological analysis of blood samples were performed using standard procedures, while physical toxicological observations were monitored daily. Amodiaquine alone, and Amodiaquine/Ciprofloxacin significantly increased the activity of Alkaline phosphatase (ALP) [P<0.05]. Ciprofloxacin alone and in combination with amodiaquine significantly (P<0.05) decreased the activity of aspartate aminotransferase (AST) with a mean value of 58.28 U/L, compared to the control 373.7 U/L). The activity of alanine aminotransferase (ALT) was significantly (P<0.05) decreased in animals administered with rifampicin alone. Uric acid concentration and g-glutamyl transferase (GGT) were significantly increased by the combination of amodiaquine and rifampicin. Mice in ciprofloxacin/ amodiaquine treatment group manifested adverse effects such as weight loss, sluggishness and loss of fur. Study animals survived beyond the duration of study despite noticeable known adverse effects associated with the individual drugs. These effects may not constitute a deterrent in the consideration of the potential usefulness of the antibiotic and antimalarial combinations.