The roles of cytochrome P450 and P-glycoprotein in the pharmacokinetics of florfenicol in chickens

Document Type : Full paper (Original article)

Authors

1 Department of Basic Veterinary Medicine, Animal College of Science and Technology, Henan University of Science and Technology, Luoyang 471023, China

2 Key Laboratory of Veterinary Chemical Drugs and Pharmaceutics, Ministry of Agriculture, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China

3 Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China

Abstract

The effects of three selective oral inhibitors, fluvoxamine (FLU), ketoconazole (KET), and verapamil (VER), on the pharmacokinetics (PK) of florfenicol (FFC) were investigated in chickens. The chickens were administered orally with saline solution (SAL), FLU (60 mg/kg), KET (25 mg/kg), or VER (9 mg/kg) for 7 consecutive days. Florfenicol was given to the chickens at a single dose of 30 mg/kg orally. Blood samples were collected from each chicken at 0 to 12 h post-administration of FFC. The plasma concentration of FFC was analyzed by high-performance liquid chromatography (HPLC). The AUC of FFC increased and the CLs of FFC decreased with oral co-administration of KET in chickens, and the Cmax of FFC increased with VER. While the AUC, the CLs and the Cmax of FFC were all invariable with FLU. These data suggested that CYP 3A played a key role in the PK of FFC in chickens, however, P-glycoprotein (P-gp) and CYP 1A did not. The results imply that the adverse drug-drug interaction may occur in the use of FFC if the co-administrated drugs are the substrates, inducers or inhibitors of CYP 3A or/and P-gp.

Keywords

References

Afifi, NA and AboEl-Sooud, K (1997). Tissue concentration and pharmacokinetics of florfenicol in broiler chickens. Br. Poult. Sci., 38: 425-428.
Anadón, A; Martínez, MA; Martínez, M; Ríos, A; Caballero, V; Ares, I and Martínez-Larrañaga, MR (2008). Plasma and tissue depletion of florfenicol and florfenicol-amine in chickens. J. Agr. Food Chem., 56: 11049-11056.
Atef, M; El-genda, YI; Amer, AMM and El-Aty, AMA (2001). Disposition kinetics of florfenicol in goats by using two analytical methods. J. Vet. Med. A Physiol. Pathol. Clin. Med., 48: 129-136.
Athukuri, BL and Neerati, P (2017). Enhanced oral bio-availability of domperidone with piperine in male Wistar rats: involvement of CYP3A1 and P-gp inhibition. J. Pharm. Pharm. Sci., 20: 28-37.
Azizi, J; Ismail, S and Mansor, SM (2013). Mitragyna speciosa Korth leaves extracts induced the CYP450 catalyzed aminopyrine-N-demethylase (APND) and UDP-glucuronosyl transferase (UGT) activities in male Sprague-Dawley rat livers. Drug Metabol. Drug Interact., 28: 95-105.
Cortright, KA and Craigmill, AL (2006). Cytochrome P450-dependent metabolism of midazolam in hepatic microsomes from chickens, turkeys, pheasant and bobwhite quail. J. Vet. Pharmacol. Ther., 29: 469-476.
Davidson Peiris, E and Wusirika, R (2017). A case report of compound heterozygous CYP24A1 mutations leading to nephrolithiasis successfully treated with ketoconazole. Case Rep. Nephrol. Dial., 7: 167-171.
Filazi, A; Sireli, UT; Yurdakok, B; Aydin, FG and Kucukosmanoglu, AG (2014). Depletion of florfenicol and florfenicol amine residues in chicken eggs. Br. Poult. Sci., 55: 460-465.
Ghoddusi, A; Nayeri Fasaei, B; Karimi, V; Ashrafi Tamai, I; Moulana, Z and Zahraei Salehi, T (2015). Molecular identification of Salmonella infantis isolated from backyard chickens and detection of their resistance genesby PCR. Iran. J. Vet. Res., 16: 293-297.
He, X and Feng, S (2015). Role of metabolic enzymes P450 (CYP) on activating procarcinogen and their poly-morphisms on the risk of cancers. Curr. Drug Metab., 16: 850-863.
Ismail, M and El-Kattan, YA (2009). Comparative pharma-cokinetics of florfenicol in the chicken, pigeon and quail. Br. Poult. Sci., 50: 144-149.
Ledwitch, KV; Barnes, RW and Roberts, AG (2016). Unravelling the complex drug-drug interactions of the cardiovascular drugs, verapamil and digoxin, with P-glycoprotein. Biosci. Rep., 36; e00309.
Lee, J; Kim, AH; Yi, S; Lee, S; Yoon, SH; Yu, KS; Jang, IJ and Cho, JY (2017). Distribution of exogenous and endogenous CYP3A markers and related factors in healthy males and females. AAPS J., doi: 10.1208/s12248-017-0090-8.
Liu, N; Guo, M; Mo, F; Sun, YH; Yuan, Z; Cao, LH and Jiang, SX (2011). Involvement of P-glycoprotein and cytochrome P450 3A in the metabolism of florfenicol of rabbits. J. Vet. Pharmacol. Therap., 35: 202-205.
NRC (1994). Nutrient requirements of poultry. 9th Rev. Edn., Washington, D.C., Natl. Acad. Press. PP: 19-34.
Pal, D and Mitra, AK (2006). MDR- and CYP3A4-mediated drug-drug interactions. J. Neuroimmune Pharmacol., 1: 323-339.
Poźniak, B; Pawłowski, P; Pasławska, U; Grabowski, T; Suszko, A; Lis, M and Świtała, M (2017). The influence of rapid growth in broilers on florfenicol pharmacokinetics-allometric modelling of the pharmacokinetic and haemo-dynamic parameters. Br. Poult. Sci., 58: 184-191.
Razmyar, J and Zamani, AH (2016). An outbreak of yolk sac infection and dead-in-shell mortality in common canary (Serinus canaria) caused by Klebsiella pneumoniae. Iran. J. Vet. Res., 17: 141-143.
Shen, J; Hu, D; Wu, X and Coats, JR (2003). Bioavailability and pharmacokinetics of florfenicol in broiler chickens. Vet. Pharmacol. Ther., 26: 337-341.
Shin, SJ; Kang, SG; Nabin, R; Kang, ML and Yoo, HS (2005). Evaluation of the antimicrobial activity of florfenicol against bacteria isolated from bovine and porcine respiratory disease. Vet. Microbiol., 106: 73-77.
Soback, S; Paape, MJ; Filep, R and Varma, KJ (1995). Florfenicol pharmacokinetics in lactating cows after intravenous, intramuscular and intramammary administra-tion. J. Vet. Pharmacol. Ther., 18: 413-417.
Suo, XB; Zhang, H and Wang, YQ (2007). HPLC determination of andrographolide in rat whole blood: study on the pharmacokinetics of andrographolide incorporated in liposomes and tablets. Biomed. Chromatogr., 21: 730-734.
Tsuji, PA and Walle, T (2007). Benzo[a]pyrene-induced cytochrome P450 1A and DNA binding in cultured trout hepatocytes-inhibition by plant polyphenols. Chem. Biol. Interact., 169: 25-31.
Verner-Jeffreys, DW; Brazier, T; Perez, RY; Ryder, D; Card, RM; Welch, TJ; Hoare, R; Ngo, T; McLaren, N; Ellis, R; Bartie, KL; Feist, SW; Rowe, WMP; Adams, A and Thompson, KD (2017). Detection of the florfenicol resistance gene floR in Chryseobacterium isolates from rainbow trout. Exception to the general rule? FEMS Microbiol. Ecol., 93(4). doi: 10.1093/femsec/fix015.
Wang, GY; Tu, P; Chen, X; Guo, YG and Jiang, SX (2013). Effect of three polyether ionophores on pharmacokinetics of florfenicol in male broilers. J. Vet. Pharmacol. Ther., 36: 494-501.
Wei, CF; Shien, JH; Chang, SK and Chou, CC (2016). Florfenicol as a modulator enhancing antimicrobial activity: example using combination with Thiamphenicol against Pasteurella multocida. Front Microbiol., 7: 389.
Yamaoka, K; Nakagawa, T and Uno, T (1978). Application of Akaike’s information criterion (AIC) in the evaluation of linear pharmacokinetic equations. J. Food Biochem., 100: 609-618.
Yang, YC; Zhang, WG; Tang, ZM; Liu, CX; Sun, RY and Yu, ZL (1988). 3P87 practical pharmacokinetics program. Information of the CPA. 5: 67.
Yasui-Furukori, N; Takahata, T; Nakagami, T; Yoshiya, G; Inoue, Y; Kaneko, S and Tateishi, T (2004). Different inhibitory effect of fluvoxamine on omeprazole metabolism between CYP2C19 genotypes. Br. J. Clin. Pharmacol., 57: 487-494.
Zhang, Y; Wang, C; Liu, Z; Meng, Q; Huo, X; Liu, Q; Sun, P; Yang, X; Sun, H; Ma, X and Liu, K (2017). P-gp is involved in the intestinal absorption and biliary excretion of afatinib in vitro and in rats. Pharmacol. Rep., 70: 243-250.
Zhou, SF (2008). Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4. Curr. Drug Metab., 9: 310-322.

Files

Share

How to cite

Statistics