Pharmacokinetics, renal clearance and metabolism of ciprofloxacin following intravenous and oral administration to calves and pigs

Abstract

SUMMARY The pharmacokinetics of ciprofloxacin, a quinoline derivative with marked bactericidal activity against gram-negative bacteria, was studied in calves and pigs following intravenous and oral administration. Ciprofloxacin was rapidly and well distributed in the body, exhibited a short elimination halflife of 2.5 h in both species, and was rapidly absorbed after oral administration (Tnax:2 to 3 h). The oral bioavailability in calves was 53 ± 14% and for 1 pig 37.3%.The renal clearance of the unbound ciprofloxacin for both species was of the same order, indicated a predominantly tubular secretion pattern, and accounted for about 46% of the total drug elimination. No complete drug mass balance could be demonstrated. Small amounts of two metabolites were detected in the urine of calves, but not in pig urine.

Pharmacokinetics of ciprofloxacin in sheep after single intravenous or intramuscular administration

“…The other parameters calculated did not reveal differences between the two routes of administration. The percentage of unaltered CIP excreted in the urine by sheep after IV administration was similar to the values obtained in calves, pigs (14), and dogs (1) after IV administration (45.6, 47.3 and 36.82% respectively). Renal clearance (C1r) in sheep was similar to that obtained in calves (0.00771/min/kg) (14), slightly lower than that in pigs (0.0156 I/min/kg), and higher than that calculated in dogs (0.0044 I/min/kg) (1).…”

“…The percentage of unaltered CIP excreted in the urine by sheep after IV administration was similar to the values obtained in calves, pigs (14), and dogs (1) after IV administration (45.6, 47.3 and 36.82% respectively). Renal clearance (C1r) in sheep was similar to that obtained in calves (0.00771/min/kg) (14), slightly lower than that in pigs (0.0156 I/min/kg), and higher than that calculated in dogs (0.0044 I/min/kg) (1). An impressive killing effect in vitro, even in the stationary growth phase, of CIP against bacterial pathogens of the gastrointestinal and respiratory tract (e.g.…”

“…has been reported. With respect to Salmonella and E. coli, it must be noted that the antimicrobial activity of CIP is at least seven-fold higher than that of flumequine (14). If it is assumed that the MIC for the target microbial organism is the therapeutic concentration and that the goal of a dosage schedule is to maintain the serum concentration over THE VETERINARY QUARTERLY, VOL 18, No 2, JUNE, 1996…”

“…In addition, CIP is reported to be the main metabolite of enrofloxacin, another antibacterial quinolone used in veterinary medicine (22). Although most of the pharmacokinetic work with this drug has been focused on humans (6,9,10,16), some studies have also been carried out on animals, such as rats, monkeys (20,21), rabbits (2,3), pigs, calves (14), horses (28), fish (13), and dogs (1,26). These studies indicate that CIP exhibits favourable pharmacokinetic properties: it is quickly distributed, and its apparent volume of distribution, greater than 1.0 1/kg in all the species studied, suggests substantial tissue penetration.…”

“…Ciprofloxacin is eliminated by both metabolism and renal excretion pathways. When orally administered, CIP has been shown to be well absorbed, with average bioavailability values of 37 and 53% in pigs and cattle, respectively (14).…”