Effect of Efflux Protein Inhibitors on Pharmacokinetics and Pharmacodynamics of Enrofloxacin in Chicken

Srividya Gullapudi; G. Srinivasarao; P. Ravikumar; Muralidhar Metta; V. Rama Devi

doi:10.5455/ijlr.20201015090255

Authors

Srividya Gullapudi Assistant Professor, Dept of pharmacology, CVSc, Proddatur, SVVU, Andhra Pradesh, INDIA
G. Srinivasarao Professor, Dept of pharmacology, NTRCVSc, Gannavaram, SVVU, Andhra Pradesh, INDIA
P. Ravikumar Professor, Dept of pharmacology, NTRCVSc, Gannavaram, SVVU, Andhra Pradesh,
Muralidhar Metta Assistant Professor & Head, Department of Animal Genetics & Breeding, Andhra Pradesh,
V. Rama Devi Professor, Dept of pathology, NTRCVSc, Gannavaram, SVVU, Andhra Pradesh, INDIA

DOI:

https://doi.org/10.5455/ijlr.20201015090255%20%20%20%20%20%20%20

Keywords:

Enrofloxacin, Glycyrrhizic Acid, Glycyrrhetenic Acid, MIC, Pharmacokinetics

Abstract

The present study was designed to investigate the effect of efflux protein inhibitors glycyrrhizic acid and glycyrrhetenic acid on pharmacodynamics and pharmacokinetics of enrofloxacin in chicken. The pharmacokinetic study was carried out in broiler chicken by randomly dividing eighteen birds into three groups of six each. Birds with enrofloxacin @10 mg.kg-1body weight orally served as control. Treatment groups received glycyrrhizic acid and glycyrrhetenic acid orally along with enrofloxacin. Blood samples were collected at predetermined time intervals upto 48 h and plasma concentrations of enrofloxacin were determined by HPLC with UV detection at 277 nm. The pharmacodynamic study was carried out by determining the MIC of enrofloxacin against E. coli ATCC25922 as per the CLSI guidelines. Cmax and AUC of enrofloxacin was enhanced in treatment groups. The MIC of enrofloxacin was improved in the presence of phytochemicals. In conclusion, glycyrrhizic acid and glycyrrhetenic acid enhanced the antibacterial activity of enrofloxacin.

References

Exner M, Bhattacharya S, Christiansen B, Gebel J, Goroncy-Bermes P and Hartemann P (2017) Antibiotic resistance: what is so special about multidrug-resistant Gram-negative bacteria? GMS Hygiene and Infection Control12:Doc05. 10.3205/dgkh000290.

Feng X, Ding L and Qiu F (2015) Potential drug interactions associated with glycyrrhizin and glycyrrhetinic acid. Drug Metabolism Reviews. Vol 47(2): 229-38.

Haritova AN, Rusenova A, Rusenov J, Schrickx L, Lashev and Fink-Gremmels J (2008). Effects of fluoroquinolone treatment on MDR1 and MRP2 mRNA expression in Escherichia coli-infected chickens. Avian Pathology 37:465–470.

Huang YP, Cao YF, Fang ZZ (2013) Glycyrrhetinic acid exhibits strong inhibitory effects towards UDP-glucuronosyltransferase (UGT) 1A3 and 2B7. Phytotherapy Research (27): 1358–1361.

Katoh M, Yoshioka Y and Nakagawa N (2009). Effects of Japanese herbal medicine, Kampo, on human UGT1A1 activity. Drug Metabolism and Pharmacokinetcs. 24:226–234.

Khan IA, Mirza ZM, Kumar A, Verma V and Qazi GN (2006). Piperine, a phytochemical potentiator of ciprofloxacin against Staphylococcus aureus. Antimicrobial agents and chemotherapy. 50(2):810–812.

Lv QL, Wang GH, Chen SH, Hu L, Zhang X, Ying G and Zhou HH (2015). In Vitro and in Vivo Inhibitory Effects of Glycyrrhetinic Acid in Mice and Human Cytochrome P450 3A4. International Journal of Environmental Research and Public Health.13(1): 84.

Masi M, Refregiers M, Pos KM and Pages JM (2017). Mechanisms of envelope permeability and antibiotic influx and efflux in Gram-negative bacteria. Nature Microbiology2:17001.

Nakagawa N., Katoh M and Yoshioka Y (2009). Inhibitory effects of Kampo medicine on human UGT2B7 activity. Drug Metabolism and Pharmacokinetics 24:490–499.

Ohene‐Agyei T, Mowla R, Rahman T and Venter H. (2014). Phytochemicals increase the antibacterial activity of antibiotics by acting on a drug efflux pump. Microbiology Open3(6):885-896.

Rao GS, Ramesh S, Ahmad AH, Tripathi HC, Sharma LD and Malik J K(2002). Pharmacokinetics of enrofloxacin andits metabolite ciprofloxacin in goats given enrofloxacinalone and in combination with probenecid. Veterinary Journal163(1):85-93.

Schindler BD and Kaatz GW (2016). Multidrug efflux pumps of Gram-positive bacteria. Drug Resistance Updates27:1–13

Silhavy TJ, Kahne D, and Walker S (2010). The bacterial cell envelope. Cold Spring Harbor perspectives in biology2(5): a000414.

World Economic Forum (2013). Global Risks Eighth Edition 28–33.

Zhang Y, Huo M, Zhou J, Xie S and PKSolver (2010). An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel. Computer Methods and Programs Biomedicine. 99(3):306-14.

Ismair MG, Stanca C, Ha HR, Renner EL, Meier PJ and Kullak-Ublick GA (2003) Interactions of glycyrrhizin with organic anion transporting polypeptides of rat and human liver. Hepatology Research 26(4):343-347.

Xiao, Y., Deng, J., Liu, X., Huang, J., Sun, Y., Dai, R., & Hong, M. (2014). Different Binding Sites of Bovine Organic Anion–Transporting Polypeptide1a2 Are Involved in the Transport of Different Fluoroquinolones. Drug Metabolism and Disposition, 42(8), 1261-1267.

Xu R, Zhang X, Yang J, Liu X, Davey AK, Wang J (2012). Effects of glycyrrhizin on biliary transport and hepatic levels of glutathione in rats. Biopharmaceutics Drug Disposition 33(5):235-45