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.

A comparative pharmacokinetic study was conducted in rainbow trout (Salmo gairdneri) and African catfish (Clarias gariepinus) following intravenous (i.v.) and intramuscular (i.m.) administration of oxytetracycline (OTC) at a dose rate of 60 mg/kg body weight. Trout and catfish were kept in aerated tap water in tanks at constant temperatures of 12 degrees C and 25 degrees C, respectively. The two- and three-compartment open models adequately described plasma drug disposition in African catfish and rainbow trout respectively, following i.v. OTC administration. Compared to catfish (COP = 86 +/- 10 micrograms/ml) an eightfold higher extrapolated zero time concentration was obtained in trout (COP = 753 +/- 290 micrograms/ml). A significant difference was observed with respect to the relatively large apparent distribution volumes (Vd(area] after i.v. OTC administration (trout, mean value: 2.1 l/kg; catfish, mean value: 1.3 l/kg). The mean final elimination half-lives of both fish species were greater than previously reported in mammals (trout, 89.5 h; catfish, 80.3 h). A mean maximum plasma concentration (Cmax = 56.9 micrograms/ml) was obtained in trout at 4 h after i.m. administration of OTC. In catfish a lower Cmax of 43.4 micrograms/ml was determined at about 7 h. No significant difference was observed with respect to bioavailability following i.m. administration of OTC (trout, 85%; catfish, 86%).

SUMMARY The plasma disposition of ciprofloxacin was studied in carp, African catfish and trout after intravenous (IV) and intramuscular (IM) administration at a dose rate of 15 mg/ kg. Pharmacokinetic analysis of IV data showed that ciprofloxacin was well distributed (distribution volume V area): 3.08 -5.59 litre/kg) and exhibited a similar elimination half-life of about 14 h in these 3 fish species. After IM administration to carp and trout a rapid absorption was noticed; the maximum ciprofloxacin plasma concentrations (mean: 3.49 and 2.37 pg/ml, respectively), were achieved within I h after injection. At the dose level applied, ciprofloxacin has potential therapeutic value for 2-5 days especially against gram-negative bacterial fish pathogens.

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