Effects of halofantrine, sulfadoxine/pyrimethamine and sulfametopyrazine/pyrimethamine on the concentration of serum phosphatases in male guinea pigs

Abstract

Background: New single and combined antimalarial therapies developed as a result of resistant strains of Plasmodium falciparum raise new toxicological concerns and considerations.

Aims: To establish and compare the dose- and time-dependent effects of three clinically used antimalarials agents on serum enzymes; alkaline phosphatase, prostatic phosphatases and acid phosphatase tartarate.

Methods: Sixty male guinea pigs of average weight 500±5 gms were placed in twelve cages of five each. They were divided into four major groups, of three subsets each. The first group (control) received only water and food. The second, third and fourth groups of three cages of five animals each were given halofantrine hydrochloride (4.0-16.0 mg/kg), sulfadoxine/pyrimethamine (12.5-50.0 mg/kg) and sulfametopyrazine/pyrimethamine (12.5-50.0mg/kg) respectively in increasing doses of half clinical, clinical and twice clinical doses. In the time-dependent experiment, the above stated protocol was repeated at different time intervals with a set of five animals each. Blood was taken at 24 hrs, 7 and 28 days respectively for biochemical analysis. Analysis of variance at 0.05 level of significance was used to test differences between groups.

Results: There were dose-dependent increases in alkaline phosphatases from14.7+0.58 to 38+2.0 IU/l (P = 0.046), 16.5+2.12 IU/l to 31.3+1.53 IU/l (p < 0.05) and 14.5+2.1 to 23+1.0 IU/l (P = 0.001) for sulfadoxine/pyrimethamine, halofantrine hydrochloride and sulfametopyrazine/pyrimethamine respectively. The time-dependent results show a progressive increase in these values maximizing on the seventh day, with a reversal (decreases) on the twenty eight day.

Conclusion: These agents produced dose- and time-dependent effects on serum phosphatases.

Keywords : Antimalarials, Serum phosphatases, Toxicity