Pharmacokinetics of enrofloxacin in sheep following intravenous and subcutaneous administration

Abstract

Enrofloxacin is a synthetic antibacterial agent of the flouroquinolone group developed exclusively for veterinary use (Altreuher, 1987). The important characteristics of the antimicrobial agent includes low host toxicity, high bioavailability, excellent tissue penetration, long serum half-life and a wide spectrum of activity against G-ve bacteria, intracellular organisms and lesser activity against G+ve organisms (Brown, 1996). It is mainly indicated for gastrointestinal, urogenital, skin and respiratory tract infections in various domestic animal species (Nielsen & Gyrd-Hansen, 1997).Flouroquinolones possess good oral bioavailability in all monogastric animals (up to 80%) but poor in ruminants (approximately 10%), which necessitates the use of parenteral routes of administration (Jenkins, 1990). The pharmacokinetics of enrofloxacin has been described in a variety of domestic animal species, but little is known about its kinetic behaviour following the subcutaneous administration in sheep, which forms an important component of Indian livestock population.The objective of this study was to determine the plasma concentrations and pharmacokinetics of enrofloxacin and its active metabolite, ciprofloxacin following the single dose intravenous and subcutaneous administration in sheep.Six crossbred healthy female sheep (weighing 25-30 kg) were quarantined for 2 weeks for use in the study. They were dewormed and maintained on concentrate, green fodder and were provided water ad libitum. The animals used for the pharmacokinetic study following intravenous administration were reused for the study following subcutaneous administration after observing a minimum washout period of 15 days.Pure technical grade enrofloxacin and ciprofloxacin were generously gifted by Intas Pharmaceuticals, Ahmedabad and Aurobindo Pharmaceutical, Chennai, respectively. Enrofloxacin (Quintas 10%; Intas Pharmaceuticals, Ahmedabad, India) was injected (5 mg/kg) in the jugular vein and in the flank region for i.v. and s.c. study, respectively. Blood samples (3 mL each) were collected by jugular indwelling catheter into heparinized glass tubes at predetermined time intervals, i.e. 0, 2, 5, 10, 15, 30, 45 min and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24 and 36 h after drug administration. Blood samples were centrifuged to harvest plasma, which was stored at )20°C until assayed. The concentrations of enrofloxacin and ciprofloxacin in plasma were simultaneously extracted (Nielsen & Gyrd-Hansen, 1997) and determined using HPLC system (Model SPD-10A, LC-10AT; Shimadzu Corporation, Kyoto, Japan) (Kung et al., 1993). Peak areas were used for quantification of the compounds. External standards were used to prepare calibration curves and determine the assay precision and recovery. Assay precision was determined by analysing two samples four times each day for intra-day assay and on four occasions 24 h apart for inter-day assay.The calibration curves prepared by spiking external standards in the pooled drug free sheep plasma were linear in the range of 0.02-3.2 ...

Pharmacokinetic behaviour of enrofloxacin and its metabolite ciprofloxacin after subcutaneous administration in cattle

“…In our study, enrofloxacin presents a similar half-life to that described in sheep (Rahal et al 2006: t 1/2β =2.60 h; MRT=3.43 h) and goats (Ramesh et al 2002: 2.84 h), however, long values of ciprofloxacin MRT were observed in our study, which could increase the efficacy. The values of elimination half-life obtained to Kaartinen et al (1995) for cows were longer than those obtained in our study.…”

Disposition Kinetics and Optimal Dosage of Ciprofloxacin in Healthy Domestic Ruminant Species

“…Rahal et al 2006). The values of C max were higher in buffaloes and cows compared to sheep and goats, while t max was almost the same in all four species with a minute difference.…”

Mycoplasma agalactiae, an Etiological Agent of Contagious Agalactia in Small Ruminants: A Review

“…Systemic use of antibiotic responds well; however, local application in advanced stages to avoid damages in mammary glands, conjunctiva, and joints should accompany systemic treatment [127, 128]. Fluoroquinolones, particularly enrofloxacin which is converted to ciprofloxacin after metabolism [129], might have less chances of resistance development. Moreover, the peak value of minimum inhibitory concentration (MIC) of ciprofloxacin is reached within few minutes in sheep [129–131] so it would be more useful in acute cases.…”

“…Fluoroquinolones, particularly enrofloxacin which is converted to ciprofloxacin after metabolism [129], might have less chances of resistance development. Moreover, the peak value of minimum inhibitory concentration (MIC) of ciprofloxacin is reached within few minutes in sheep [129–131] so it would be more useful in acute cases. The use of traditional antibiotics in acute cases is followed by the long acting preparations which have vital role in the subclinical and chronically affected animals.…”