Activity of epiroprim (Ro 11-8958), a dihydrofolate reductase inhibitor, alone and in combination with dapsone against Toxoplasma gondii

Author:

Chang H R1,Arsenijevic D1,Comte R1,Polak A1,Then R L1,Pechère J C1

Affiliation:

1. Department of Microbiology, Faculty of Medicine, National University of Singapore.

Abstract

We examined the effect of epiroprim (Ro 11-8958), a dihydrofolate reductase inhibitor, alone and in combination with dapsone, against Toxoplasma gondii. In vitro, the anti-T. gondii effects of epiroprim and dapsone were observed at nanogram-per-milliliter levels when a 72-h uracil assay and an infection rate of one parasite per 120 macrophages were used. In combination, these drugs exerted a synergistic effect that, however, was only parasitostatic. In a model of acute infection, mice were infected intraperitoneally with 10(4) parasites of the RH strain of T. gondii and were treated for 14 days by gavage (therapy divided into two daily dosages), starting 24 h after infection. Used alone, dapsone and epiroprim, each at a dose of 50 mg/kg of body weight per day, protected 10 and 0% of the mice, respectively. When these drugs were administered simultaneously, a 100% survival rate was observed. Pyrimethamine-sulfadiazine (4 and 250 mg/kg/day, respectively) protected 100% of the mice. A 3-week therapy of chronically infected mice with either epiroprim (50 mg/kg/day), dapsone (50 mg/kg/day), or pyrimethamine (15 mg/kg/day) reduced the numbers of T. gondii cysts and the inflammation in their brains. A combination of epiroprim and dapsone, both at 50 mg/kg/day, further reduced the number of brain cysts in comparison with the number after the corresponding monotherapies. Epiroprim may have a role in the prophylaxis or therapy of human toxoplasmosis, especially when combined with other drugs active against T. gondii, such as dapsone.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Reference26 articles.

1. Azithromycin, a macrolide antibiotic with potent activity against Toxoplasma gondii;Araujo F. G.;Antimicrob. Agents Chemother.,1988

2. Remarkable in vitro and in vivo activities of the hydroxynapthoquinone 566C80 against tachyzoites and cysts of Toxoplasma gondii;Araujo F. G.;Antimicrob. Agents Chemother.,1991

3. .Chang H. R D. Arsenijevic A. Polak R. Then and J.-C. Pechere. 1993. Program Abstr. 33rd Intersci. Conf. Antimicrob. Agents Chemother. abstr. 386.

4. In vitro and in vivo effect of doxycycline on Toxoplasma gondii;Chang H. R;Antimicrob. Agents Chemother.,1990

5. Activity of minocycline against Toxoplasma gondii infection in mice;Chang H. R;J. Antimicrob. Chemother.,1991

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