Enantiospecific antitrypanosomal in vitro activity of eflornithine

The polyamine synthesis inhibitor eflornithine is a recommended treatment for the neglected tropical disease Gambian human African trypanosomiasis in late stage. This parasitic disease, transmitted by the tsetse fly, is lethal unless treated. Eflornithine is administered by repeated intravenous infusions as a racemic mixture of L-eflornithine and D-eflornithine. The study compared the in vitro antitrypanosomal activity of the two enantiomers with the racemic mixture against three Trypanosoma brucei gambiense strains. Antitrypanosomal in vitro activity at varying drug concentrations was analysed by non-linear mixed effects modelling. For all three strains, L-eflornithine was more potent than D-eflornithine. Estimated 50% inhibitory concentrations of the three strains combined were 9.1 μM (95% confidence interval [8.1; 10]), 5.5 μM [4.5; 6.6], and 50 μM [42; 57] for racemic eflornithine, L-eflornithine and D-eflornithine, respectively. The higher in vitro potency of L-eflornithine warrants further studies to assess its potential for improving the treatment of late-stage Gambian human African trypanosomiasis.
Author summary The neglected tropical disease human African trypanosomiasis is lethal unless treated. One of the treatments for the late stage–i.e. when parasites have invaded the central nervous system–of Gambian human African trypanosomiasis is the drug eflornithine, which is dosed as 50:50 racemic mixture of the two enantiomers L-eflornithine and D-eflornithine. This study showed that L-eflornithine was better than D-eflornithine at inhibiting the growth of parasites in vitro. The 50% inhibitory concentration for L-eflornithine was 5.5 μM in comparison to 50 μM for D-eflornithine. This higher in vitro potency for L-eflornithine warrants further studies to assess its potential as an improved treatment for late-stage Gambian human African trypanosomiasis.