Pharmacokinetics Of Gamithromycin Injection In Cattles

Gamithromycin, a novel semi-synthetic macrolide antibiotic noly for animal uses, is produced by fermentation and organic synthesis. By disrupting RNA-dependent protein synthesis, gamithromycin has both bacteriostatic and bactericidal effects. Gamithromycin is approved for the treatment and prevention of bovine respiratory disease (BRD) casused by Mannheimia haemolytica, Pasteurella multocida and Histophilus somni in non-lactating cattle. Gamithromycin has a good pharmacokinetic characteristics such as quicker absorption and higher bioavailability. That is to say, gamithromycin can reach a rather high concentration in lung tissues, and then achieve a better treatment of BRD. Besides, the toxic of gamithromycin is less which causes a little side effects on target animals. Moreover, residue in edible tissues is few, which is good for consumers.This experiment aimed to study the pharmacokinetic and bioavailability of domestic gamithromycin injection subcutaneously administered in non-lactating dairy calves, and Pharmacokinetic parameters are obtained. The study has important significance to guide the clinical rational use of drugs, new drug evaluation, individualized medicine, and improved pharmaceutical dosage form, it also has important reference value to predict the accumulation characteristics and residue elimination of drug in animals.In a parallel experiment, twelve healthy non-lactating cattles(6♂+6♀) were randomly divided into two groups. A single dose of 15% gamithromycin injection (6 mg/kg) was administered to a group of animals via subtaneous injection, while 15% Gamithromycin injection at dose of 3 mg/kg was administrated to another group of animals via intravenous injection. Blood samples were collected at predetermined time point after administration, and Gamithromycin concentration in plasma was tested by ultra performance liquid chromatography (UPLC)-MS/MS, with a mobilephase of lOmM ammonium acetate:methanol(V:V=30:70). Pharmacokinetic characters were anlyzed by Winnonlin5.2 software.After a single intravenous injection of gamithromycin injection, the main pharmacokinetic parameters of gamithromycin were as follow:the mean elimination half-life (T1/2β), the mean area under the curve (AUC), the mean residence time (MRT) and Vz was 54.29 h,3576.90 h·ng/mL, 34.14 h,63814.48 ml/kg, respectively. The clearance rate (Clobs) was high with a value of 824.27 ml/h/kg. After a single subtaneous injection of Gamithromycin injection, the mean elimination half-life (ti/2β) was 49.55 h, and the tmax and Cmax were about 1 h and 706.20 ng/mL. The MRT was about 23.85 h while mean AUC was approximately 7428.81 h-ng/mL. The bioavailability was 103.84% concluded from both the groups. Results indicate that, the distribution of gamithromycin in cattle was extensive and rapid and elimination was slow with a rather long T1/2β Obiviously, subcutaneous administration of gamithromycin can achieve a quick and efficient absorption rate in cattles.