The hormonal effects of halofantrine hydrochloride (Halfan), sulfametopyrazine/pyrimethamine (Metakelfin) and sulfadoxine/pyrimetamine (Fansidar) in male guinea pigs

Abstract

Background: The incidence of male factor infertility has been described by certain authors to be on the increase. The male reproductive function is highly sensitive to many xenobiotics such as drugs (Halofantrine hydrochloride, sulfadoxine/pyrimethamine and sulfametopyrazine/pyrimethamine) used in malaria therapy. Thus necessitating the investigation of the effects these agents on reproductive function.

Aim: To compare the effects of Halofantrine hydrochloride, sulfadoxine/pyrimethamine and sulfametopyrazine/pyrimethamine on the hormonal and sperm parameters.

Method: In 60 guinea pigs (500 ± 5 gm), the effect of different doses of halofantrine hydrochloride (4.0-16.0 mg/kg), sulfametopyrazine /pyrimethamine (12.5 mg/kg-50 mg/kg) and sulfadoxine /pyrimethamine (12.5 mg/kg-50 mg/kg) were studied. In n=120 animals, the effect of time (0, 24hrs, 7days and 28 days) to a single dose of each of these agents was studied. At the end of these times blood samples were obtained from the animals and hormonal analysis and sperm characteristics were investigated.

Results: Sulfadoxine/pyrimethamine and sulfametopyrazine/pyrimethamine caused statistically significant dose-dependent decreases in serum prolactin levels from 127.5 + 21.1units to 95+ 5.0 and 90.3+ 7.94 units respectively at clinical doses. Halofantrine comparatively had little or no effect on prolactin. The order of activity on prolactin was sulfadoxine/pyrimethamine > sulfametopyrazine/pyrimethamine > halofantrine  hydrochloride.  Sulfadoxine/pyrimethamine (25 mg/kg) produced a statistically significant dose-dependent reduction in epididymal sperm number (ESN) from 75.33 ± 3.76 × 106  to 20.33 x 1.86× 106 million. The order of activity on ESN was sulfadoxine/pyrimethamine > sulfametopyrazine/pyrimethamine > halofantrine hydrochloride.

Conclusion: These differences may be due to the oxidative reactivity of these drugs and may explain some clinical symptoms experienced during and post treatment.

Key words: Halofantrine hydrochloride, Hormonal effects, Guinea pigs, Sperm count