No abstract

The objective of this pharmacokinetic study was to investigate absorption, distribution, elimination and bioavailability of oxytetracycline (OTC) in carp, Cyprinus carpio L., after different routes of administration. OTC was administered intravenously (i.v.), intramuscularly (i.m.) and orally at 60 mg/kg body weight. OTC levels were determined in plasma and several tissues. Analysis of the plasma drug concentration-time curves following i.v. OTC injection revealed three distinct phases. A three-compartment open model was used to derive pharmacokinetic parameters. Compared to mammals, a very extended final elimination half-life was observed (139-8±38-l h). Followmg i.m. OTC administration, C^,, was 56-8±10-9//gOTC/mI at 14 h post-injection. The Vd area was 2-l±0-66 I/kg. Extreme differences were observed with respect to bioavailability following i.m. and oral administration; approximately 80 and 0-6%, respectively, Eollowing i.m. injection tissue OTC determinations revealed that the drug was accumulating in pronephros, bone tissue and scales. After 21 days the OTC concentrations were 2-9±0-8, 5-2±0-3 and 4-7+3-1/^g/ ml, respectively. In tissue samples from the dorsal region (muscle), including the injection site, OTC could not be demonstrated at that time. The pharmacokinetic data are discussed in relation to the susceptibility of the immune system of fish for modulation.

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.

SUMMARY After intramuscular (mi) administration (dose 20 mg/kg) of three 20%(Terramycin®/LA (product A), Alamycin® LA (product B) and Terra lon 20% LA (product C)) and two 10% oxytetracycline (OTC) formulations (Engemycin® 10% (product D) and Oxyject® 10% (product E)), to calves, pigs and sheep, the .OTC residue concentrations were determined in organs, muscle, fat, plasma, urine and at the injection sites at 10 days post injection (p.i.). At that time the irritation at the injection site was studied, too. The three 20%-formulations (products A, B, C) and one 10%-formulation (product E) induced considerable local irritation in and between the muscles. This was most pronounced in calves and pigs; in sheep the extent of irritation was limited. Ten days after administration of formulations A, B, C and E, OTC residues were found in organs and the OTC recovery at the injection sites varied widely among the three species. Following hvf injection of product D minimal tissue irritation and no OTC residues could be detected at the injection site at 10 days p.i. The differences in local tissue irritation and the residue state of the carcass (including injection site) are related to the various solvent systems used in the formulations.

In 1996, the European Union established provisional maximum residue limits (MRL) for gentamicin, neomycin, streptomycin and dihydrostreptomycin in milk and tissue (0.1-5 mg kg-1). For the detection of these four aminoglycosides, three enzyme linked immunosorbent assays (ELISA) for applications in milk and kidney were developed. The screening of defatted and diluted milk resulted in limits of determination (LDM) of < 0.01 mg l-1. Kidney samples were deproteinized with a trichloroacetic acid solution (3%) and after filtration and the addition of buffer, aliquots were used in the ELISA. The LDM of the four aminoglycosides in kidney were < 0.05 mg kg-1. The ELISA were found suitable for the semi-quantitative screening of milk and kidney for the presence of the four aminoglycosides far below the MRL levels. In randomly taken milk samples (n = 776) and in kidneys derived from healthy pigs (n = 124), the aminoglycoside residues found were far below their established MRL. In eight out of the 94 kidney samples obtained from diseased animals after emergency slaughter, aminoglycoside residues were above the MRL.