Dr. Sanis JulietVEENA2024-02-062024-02-062023-02-06https://krishikosh.egranth.ac.in/handle/1/5810206723Meropenem is a carbapenem class of antibiotics with a broad spectrum of activity against gram-positive, gram-negative, and anaerobic bacteria. Cationic antimicrobial peptides (AMPs) are a potential class of chemicals that can be used in conjunction with conventional antibiotics to treat a variety of infections. Imprudent use of antibiotics without knowledge of its pharmacokinetics and pharmacodynamics is one of the reasons for development of resistance. And in poultry, studies on the pharmacokinetics of meropenem alone or its combination with other antimicrobial agents are meagre when compared to the other species. Hence, the present study was conducted to investigate the pharmacokinetics of meropenem alone and in presence of a synthetic cecropin A-(1-7) melittin (CAMA) following single intravenous administration of 24 mg/kg in broiler chicken. Blood and intestinal contents were collected at predetermined time intervals after administration alone and in combination with CAMA at 0.65 mg. The concentration of meropenem in plasma and intestinal contents were analysed by HPLC. The pharmacokinetics of meropenem, as well as meropenem in combination with CAMA was best described by a two-compartmental model for plasma samples whereas for the intestine it followed a non-compartmental model. Meropenem was detected in the plasma of birds till 4 h when administered alone whereas in combination with CAMA up to 48 h. Kinetic parameters of both the groups indicated a rapid rate of distribution reinforced by the high tissue-to-blood ratio, whereas, in combination with CAMA significantly higher values were noted for Cp(max), AUC, T1/2β and MRT. The concentration in the intestinal content was lower than the plasma for initial time points and was maintained at almost a steady level till 48 h with approximately half of the initial plasma concentration indicating that meropenem was actively secreted into the intestine following intravenous administration. The study thus revealed that the presence of CAMA significantly altered the pharmacokinetic behaviour of meropenem in healthy broiler birds showing a rapid, but limited distribution with slower elimination.EnglishThesis