VENKATA RAO .K.V (MAJOR)SRIVIDYA .GASWANI KUMAR .KANJANEYULU POTLURI2024-07-072024-07-072024-01https://krishikosh.egranth.ac.in/handle/1/5810211554Drug interaction play a significant role in modulating the pharmacological effect elicited by the drugs in various clinical conditions. Ciprofloxacin, a commonly used quinolone group of antibacterial agent used widely in livestock species as well as in human beings due to its broad spectrum of antibacterial activity. Some of the research findings revealed that vitamin D, Carica papaya alter the kinetic behaviour of ciprofloxacin. This created an interest to study the kinetic behaviour of ciprofloxacin in the presence of vitamin B1 (thiamine) and selected essential amino acid phenylalanine. It is very common that B-complex group of vitamins and dietary supplements with antioxidant activity are prescribed along with antibacterial agents. Thiamine (vitamin B1) is one of B-complex group of vitamin with antioxidant activity, plays a crucial role in energy metabolism, growth, development and functioning of cells. Phenylalanine acts as precursor for tyrosine, dopa (dihydroxyphenylalanine) and catecholamine. The conversion of phenylalanine to tyrosine is facilitated by the enzyme phenylalanine hydroxylase. The sources of phenylalanine include foods like wheat germ, oats, dairy products, and various meats. By keeping this in view the present study was designed to determine the “Interplay of vitamin B1 and selected essential amino acids on the antibacterial activity and pharmacokinetics of ciprofloxacin in rabbits” by microbiological assay. Minimum inhibitory concentration (MIC) of ciprofloxacin using MTCC 443 was calculated by microbroth dilution technique. The MIC end point in the current study was 0.06 µg.mL 1against E.coli MTCC 443. The pharmacokinetic study was conducted in rabbits following single oral administration of ciprofloxacin. Rabbits weighing 2-4 kg randomly divided into 5 groups of 6 each. Group I served as control without any treatment. Group II served as ciprofloxacin control whereas Group III, IV and V rabbits were coadministered with thiamine (80 mg.kg-1), phenylalanine (48 mg.kg-1), combination of thiamine & phenylalanine along with ciprofloxacin (40 mg.kg-1) orally. Blood samples were collected at predetermined time intervals from 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12 h and plasma was used for estimation of ciprofloxacin through bioassay. Results obtained from the experiment revealed that rabbits of Group III, IV & V showed improved levels of Cmax are 4.74±0.17, 3.00±0.22, 2.18±0.12 µg.mL-1 and AUC are 20.30±5.19, 10.09±1.48, 12.85±1.34 µg.h.mL-1 respectively when compared to values of Cmax and AUC are 2.10±0.14 and 5.90±0.81 µg.h.mL-1 in Group II rabbits respectively. Among the different interventions thiamine coadministered with ciprofloxacin showed improved antibacterial activity, bioavailability and duration of action of ciprofloxacin in rabbits. There is no much significant role of combination of thiamine and phenylalanine (Group V) coadministration with ciprofloxacin when compared to only thiamine coadministered with ciprofloxacin (Group III) and only phenylalanine with ciprofloxacin (Group IV) on kinetic behaviour of ciprofloxacin in rabbits. PK-PD integration of the present study revealed that Cmax:MIC>8, AUC:MIC>125 in Group III, IV and V which implies that the coadministration of vitamin B1 and phenylalanine and their combination improves the antibacterial activity and reduce the development of resistance at the selected dose of ciprofloxacin.EnglishThesis