| Abstract: | The present studies were conducted to compose an injectable solution of colistin sulfate containing local anaesthesia, antioxidant and other additions. Results showed that the novel preparation was stable either to heat or to light. The term of validity of the preparation was 2 years at room temperature.The preparation containing 25.0 mg ml-1 colistin sulfate showed no local tissue irritation, but the concentration of 50. 0 mg ml-1 colistin sulfate showed obvious local tissue irritation. Result of acute toxicity test showed that the LD50 of intramuscular injection in mice was 38. 72 mg kg-1 , and oral LD50 was 431.39 mg kg-1. The evidence of neurotoxicity was observed in mice in the acute toxicity test. A dose of 10.0 mg kg-1 b.w. or 15:0 mg kg-1 b.w. was administered intramuscularly to piglet once daily for 5 days. No changes were detected in the piglet body except for the slight epithelial tissue's granular degenerations in the kidney and liver at the dose of the 10. 0 mg kg-1. While at the dose of 15.0 mg kg-1 , the obvious neurotoxicity was observed at 4 - 5 days. The epithelial tissues in the kidney and liver showed moderate granular degenerations, especially in the tubuli renales cells. Blood cell's morphosis indexes were normal. With relation to liver's function, the indexes went beyond the normal scope. But with relation to kidney's function, the indexes showed mostly normal.When the preparation was separately administered into muscle(i. m. ) in piglets with the dose of 2.5 and 5.0 mg kg-1 b. w, whose Cmax were 3.73±0. 28 and 6. 40±0. 18 μg ml-1; Tmax were 32±1.5 and 34±1.8min;t1/2β were 256±14 min and 264±29 min, respectively. t1/2β was 251±13 min for the injection given into aural vein(i. v. ) with the dose of 2.5 mg kg-1 b.w.. Samples of the experimentally determined plasma concentration of colistin sulfate generated two-exponential model with first-order absorption. The mean absolute bioavailability coefficient of 2.5 and 5.0 mg kg-1 b. w. (i. m. ) were 98. 30 and 88.54%, respectively. The high bioavailability and the long maintaining time of the valid blood-drug concentration showed that the injectable solution was suitable for i.m. in pigs, whose recommended dose was 2.5 mg kg-1 b. w., twice daily. |
