Some Pharmacological Aspects of Simultaneous Administration of Diminazene aceturate and Sulphadimidine Sodium in Donkeys

Abstract

This study was conducted to evaluate the safety of repeated administration of Diminazene aceturate and/or Sulphadimidine sodium in donkeys. For this purpose two experiments were conducted to evaluate the effect of medication on some haematological indices as well as liver and kidney functions. In the first experiment a total number of 18 male donkeys, 4-10 years of age, were divided into three groups. Treatment was randomized among groups. The first group received Diminazene aceturate at the manufacturer dose of 3.5 mg/kg injected intramuscularly for three successive days, the second group was subjected to treatment with Sulphadimidine sodium at the manufacturer recommended dose of 3 ml/10 kg for three successive days, while the third group subjected to a combination of the two drugs Diminazene aceturate and Sulphadimidine sodium at the same dose level mentioned above for three successive days. Following each treatment animals were monitored for two hours to report any side and/or adverse effects. Blood samples were collected at pre-determined time points, directly from jugular vein, and divided into two portions one with anticoagulant to examine some haematological indices: haemoglobin concentration, RBCs count and Packed cell volume. The other portion was kept without anticoagulant for serum harvesting. Serum was examined to evaluate the effect of the drugs on the liver and kidney functions: total protein, albumin, Bilirubin, urea, creatinine, and the activities of liver enzymes (Alanine aminotransferase ALT and Aspartate aminotransferase enzyme AST), calcium, phosphorus, sodium, and potassium. Results obtained in the first experiment showed that following Diminazene aceturate administration, donkeys immediately and up to two hours monitoring period showed some sort of irritation as well as oedema at the injection site. The PCV values were significantly (P<0.05) decreased in the group received Sulphadimidine sodium for three successive days, while RBCs count and haemoglobin level showed no significant (P<0.05) fluctuation during the study period in the three treated groups. A decrease in total protein concentration was observed both in the Diminazene aceturate and the combination treated groups. Albumin increased significantly (P<0.05) following the second dose and continued to be like that up to the end of the study period in the group that received Diminazene aceturate. A significant increase (P<0.05) in Serum bilirubin was observed in both the Diminazene aceturate and the combination group. While, administration of Sulphadimidine sodium induced no significant (P>0.05) increase in bilirubin concentration. The activities of ALT and AST showed significant (P<0.05) increase following treatment in the treated groups. Significant increase (P<0.05) in urea level was observed in first three days following treatment in the combination group; while, administration of Diminazene alone or in combination with Sulphadimidine sodium to donkeys for three successive days resulted in significant (P<0.05) decrease in creatinine level. Calcium level decreased significantly (P<0.05) in the donkeys received Diminazene for three successive days. Serum phosphorus level increased once in the Sulphadimidine group (day 5) and decreased at three time points in the combination group. Donkeys in the three treated groups exhibited significant (P<0.05) increase in sodium level during the study period. Potassium level increased significantly (P<0.05) in the groups that received Diminazene and Sulphadimidine sodium, respectively. In the second experiment a total number of 24 male donkeys, 4-10 years of age, were divided into four groups each of six animals. Animals were subjected to starvation for 48 hours before the start of treatment. Donkeys in the first group remained untreated (control group), the three other groups were subjected to the same treatment regimens described above in the first experiment. Top of Form

The same as in the first experiment animals treated in the second experiment, showed irritation and oedema at injection site. In the control group immediately following fasting PCV (%) decreased significantly (P<0.05) in the 3rd and 5th day and continued with non significant decrease up to the end of the experiment period. Simultaneous significant decrease in PCV (%) was observed following injection of Diminazene up to the 5th day of treatment, while in the group treated with Sulphadimidine sodium a significant decrease was observed following fasting and remained with no significant difference during the treatment period. The combination of Diminazene and Sulphadimidine sodium resulted in non significant change in PCV (%). A subsequent decrease in RBCs count was observed in the different treatment groups as well as in the control group immediately following injection of the first dose, while Sulphadimidine sodium and the control groups exhibited another significant decrease at the 2nd and 3rd days, respectively. A significant increase in Hb concentration was observed in the control and Sulphadimidine sodium treated groups, while the other two treatment groups exhibited no significant fluctuation in Hb concentration when compared with pre-treatment level. A significant increase in total protein concentration was observed in the Diminazene and the combination groups, respectively. While the Sulphadimidine treated group showed significant decrease following the 3rd injection. Significant decrease in albumin concentration was observed in the control group and Sulphadimidine sodium treated group, while Diminazene treated group exhibited significant increase during fasting period and continued with no significant increased level up to the end of the experiment. Although a significant (P<0.05) decrease in bilirubin concentration was observed in the control group, a significant (P<0.05) increase in bilirubin concentration was observed in the first two days following treatment in the groups treated with Diminazene and Sulphadimidine sodium. While in the combination group there was no significant change. There was significant increase in ALT activity in the groups treated with Diminazene and the combination while in the group treated with Sulphadimidine sodium there was no significant increase. There was significant increase in AST activity in all treatment groups when compared with pre-treatment level following administration of drugs. Urea level increased significantly following treatment with Diminazene, while a no significant increase was observed in the other two treated groups. Slight significant increase in creatinine concentration was observed in the first two days of treatment in the groups treated with Diminazene and Sulphadimidine sodium, while the increase continued up to the end of the experiment in the combination treatment group. A significant (P<0.05) increase in calcium concentration was observed in the groups treated with Sulphadimidine sodium and the combination. A significant increase in phosphorus concentration was observed only in the group treated with Sulphadimidine sodium while, in the other two treatment groups there was significant decrease. Although there was significant decrease in the sodium level in the control group, there was only simultaneous decrease in the group treat with Diminazene. A prominent significant increase in potassium level was observed in the groups treated with Diminazene and Sulphadimidine sodium respectively. By the end of the experiment at day 10 almost all the groups showed no significant difference with pre-treatment values for all the haematological indices as well as the blood biochemical constituents investigated. These results indicated that the new regimen using Diminazene aceturate with three successive doses with or without Sulphadimidine sodium did not show any symptoms of toxic lineage because all the changes that have occurred in the levels of these parameters were within the normal range in donkeys previously reported by several researchers.