An animal model of clinical kinetic analyzed to diminazene aceturate in subjects with Tripanosoma infection.

Diminazene aceturate has been reported to inhibit the reverse transcriptase activity by intercalating action mechanism of a number of protozoon eucaryot parasitic like Trypanosoma species. The phamacokinetics of diminazene in the blood plasma of five infected goats treated with single intramuscular doses of 7 mg diminazen base kg-1 body weight was investigated. The concentrations of the drug were determined by reverse phase high performance liquid chromatography. Results show that the mean (± SD) Absorption, Distribution, Metabolism and Excretion (ADME) of the drug plasma followed a tri-exponential process with Ka (minutes-1) were obtained at 5.10-2 ± 26.10-3, α (minutes-1), K12 (minutes-1) and K21 (minutes-1) were obtained at 18.10-3 ± 1.10-2, 14.10-3 ± 1.10-2 and 1.10-3 ± 1.10-3. The mean values of β (minutes-1) and K13 (minutes-1) were obtained at 1.4.10-4 ± 4. 10-5 and 3.10-3 ± 2.10-3. The mean values of Tmax (minutes) and Cmax (µg.ml-1) were obtained at 53.71 ± 30.61 and 13.40 ± 8.13. The mean values of Vds (L), Cl (ml.minutes-1), T1/2β(hours-1) and AUC0→∞ (µg.L-1.minutes) were obtained at 4.91 ± 3.12, 14.29 ± 4.08, 94.91 ± 33.23 and 12.680 ± 2.722.

Effects of ethidium bromide and berenil on protein synthesis

The effects of ethidium bromide, an intercalating dye and berenil, a nonintercalating dye on the biological activities of Escherichia coli ribosomes have been studied. Ethidium bromide treatment drastically reduced both enzymatic and nonenzymatic initiation complex formation, enzymatic as well as nonenzymatic binding of phenylalanyl tRNA, peptidyl transferase, GTPase as well as the overall protein synthesising activity as measured by the poly U-dependent polymerization of phenylalanine. On berenil treatment, however, only enzymatic formation of the initiation complex is marginally reduced. Other reactions are not markedly affected except the enzymatic phenylalanyl tRNA binding which is slightly decreased only at high Mg2+ concentration; the treated ribosome has lowered polymerizing activity at sub-optimal Mg2+ concentration (10 mM). Although it has already been shown in this laboratory that treatment with either dye leads to the unfolding of the structure of the ribosome, the present studies indicate that berenil treatment does not alter the structure of the ribosome drastically in contrast to ethidium bromide treatment.