Pharmacokinetics of sulphadimidine in carp (Cyprinus carpio L.) and rainbow trout (Salmo gairdneri Richardson) acclimated at two different temperature levels.

The influence of temperature (10 degrees C and 20 degrees C) on pharmacokinetics and metabolism of sulphadimidine (SDM) in carp and trout was studied. At 20 degrees C a significantly lower level of distribution (Vdarea) and a significantly shorter elimination half-life (T(1/2)beta) was achieved in both species compared to the 10 degrees C level. In carp the body clearance parameter (ClB(SDM)) was significantly higher at 20 degrees C compared to the value at 10 degrees C, whereas for trout this parameter was in the same order of magnitude for both temperatures. N4-acetylsulphadimidine (N4-SDM) was the main metabolite of SDM in both species at the two temperature levels. The relative N4-SDM plasma percentage in carp was significantly higher at 20 degrees C than at 10 degrees C, whereas there was in trout no significant difference. In neither species was the peak plasma concentration of N4-SDM (Cmax(N4-SDM)) significantly different at two temperatures. The corresponding peak time of this metabolite (Tmax(N4-SDM)) was significantly shorter at 20 degrees C compared to 10 degrees C in both carp and trout. In carp at both temperatures, acetylation occurs to a greater extent than hydroxylation. Only the 6-hydroxymethyl-metabolite (SCH2OH) was detected in carp, at a significant different level at the two temperatures. Concentrations of hydroxy metabolites in trout were at the detection level of the HPLC-method (0.02-micrograms/ml). The glucuronide metabolite (SOH-gluc.) was not detected in either species at the two temperatures.

Comparative pharmacokinetics of oxytetracycline in rainbow trout (Salmo gairdneri) and African catfish (Clarias gariepinus).

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%).

Pharmacokinetics of ciprofloxacin in carp, African catfish and rainbow trout.

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 Vd(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 micrograms/ml, respectively), were achieved within 1 h after injection. At the dose level applied, ciprofloxacin has potential therapeutic value for 2-5 days especially against gram-negative bacterial fish pathogens.

Plasma disposition and renal clearance of sulphadimidine and its metabolites in laying hens.

Plasma disposition of sulphadimidine (SDM) and its metabolites was studied in laying hens after 100 mg SDM kg-1 doses were administered as a single intravenous dose, a single oral dose and multiple oral doses once daily for five consecutive days. SDM was extensively metabolised by acetylation and hydroxylation. In plasma, the metabolite observed with the highest concentration was N4-acetylsulphadimidine (N4-SDM) followed by hydroxymethylsulphadimidine (CH2OH) and 5-hydroxysulphadimidine. Following intravenous administration a biphasic elimination (as seen for a capacity limited reaction) pattern for SDM and its metabolites was observed. Multiple (5x) SDM dosing revealed plasma SDM concentrations ranging between 7 and 108 micrograms ml-1; within 96 hours of termination of the multiple SDM dosing, the plasma SDM concentration was below 0.01 micrograms ml-1. The renal clearances of N4-SDM and the hydroxy metabolites were approximately 10 times greater than that of SDM. The SDM mass balance (faecal/urinary recovery) showed a loss of 56 per cent after intravenous dosage and of 67 per cent after a single oral dosage; the hydroxy metabolites accounted for the highest percentage in faeces/urine. Thus additional metabolic pathways must exist in laying hens.

Relationship between cytologic changes in bronchoalveolar lavage fluid and weight gain in calves with gastrointestinal nematodes and lungworms.

Two of three groups of 10 calves each were infected with either 100,000 infective larvae (L3) of Ostertagia spp. and 100,000 L3 of Cooperia spp. or with 4000 L3 of Dictyocaulus viviparus, respectively, at the age of 14 weeks. The third group was not infected. After treatment with an anthelminthic five calves from each group were challenged with either 100,000 L3 of Ostertagia spp. and 100,000 L3 of Cooperia spp. or 4000 L3 of Dictyocaulus at the age of 20 weeks. The calves were 25 weeks old when slaughtered. Total and differential cell counts were determined in bronchoalveolar lavage fluid and showed that neutrophils were the most frequent and eosinophils the least frequent cell present. There was a significant negative relationship between eosinophil levels and weight gain of the calves.

Residues of sulphadimidine and its metabolites in eggs following oral sulphadimidine medication of hens.

The depletion of sulphadimidine (SDM) and its N4-acetyl and hydroxy metabolites was studied in eggs laid by hens after administration of either a single or multiple oral dosages of 100 mg SDM/kg. During medication and until 1 day after the last dose, the SDM and its metabolite concentrations in the egg white exceeded those in the egg yolk and reflected the plasma levels. In the period starting 2 days after the (last) dosage, the SDM concentration in the yolk became higher than in the egg white, and the drug depletion curves ran parallel. The mean maximum amount of SDM found in the whole egg was 1500 micrograms after a single and 1280 micrograms after multiple dosage. In eggs, traces of the N4-acetyl and 6-methylhydroxy metabolites could be detected (mainly in the egg white), and their concentrations were approximately 40 times lower than those of the parent drug. A highly significant correlation (P less than 0.005) was found between the development stage of the oocyte at the time of (last) medication and the amount of SDM found in the egg that developed from it. A period of 7 or 8 days after the (last) dosage of 100 mg SDM/kg/day is required to obtain SDM levels below 0.1 micrograms/g egg.

Fish and antibiotics: pharmacokinetics of sulphadimidine in carp (Cyprinus carpio).

Pharmacokinetics, metabolism and clearance of sulphadimidine (SDM) were studied after a single intraperitoneal injection of SDM in carp at 20 degrees C. SDM was acetylated and hydroxylated to a small extent. The main metabolite was N4-acetyl derivative amounting only 2% of the total drug dose excreted; hydroxylation was less important (0.41% of the dose). The elimination half-life for SDM in carp was 17.5 h. The clearance values for SDM and its metabolites were equivalent. The importance of pharmacokinetic studies in different fish species is discussed.

The influence of antibiotics on the immune system. III. Investigations on the cellular functions of chicken leukocytes in vitro.

Tetracyclines are bacteriostatic antibiotics widely used in veterinary medicine. It is reported here that the tetracycline analogue oxytetracycline (OxyTC) interferes with the mitogenic response of chicken leukocytes. A dose-dependent suppression of lectin stimulation of peripheral blood and spleen leukocytes was observed. The kinetics of the DNA-synthetic activity were seriously affected. The antimicrobial agent does not seem to have any effect on interleukin 2 (IL-2) production, whereas the uptake of 3H-thymidine by IL-2-dependent T cell blasts was severely reduced. It is concluded that the T cell blast is the target for OxyTC.

The influence of antibiotics on the immune system. II. Modulation of fish leukocyte responses in culture.

We report the immunomodulating effect of two tetracycline analogues (oxytetracycline and doxycycline) on mitogenic and allogeneic stimulation of carp (Cyprinus carpio) leukocytes in vitro. Both drugs interfered with 3H-thymidine incorporation into the DNA of phytohaemagglutinin-stimulated pronephric leukocytes in a dose-dependent manner. Low concentrations of oxytetracycline delayed the mitogenic response, but did not reduce it. In addition, several other antibiotics were tested for their possible interference with blastogenesis.

Phylogeny of interleukins: growth factors produced by leucocytes of the cyprinid fish, Cyprinus carpio L.

Supernatants of phytohaemagglutinin (PHA)-activated pronephric leucocytes from carp (Cyprinus carpio L.) contain a lymphocyte growth factor which can induce a proliferative response of purified lymphoblasts but not freshly isolated leucocytes. The growth-promoting activity can be reduced by absorbing the supernatant with mitogen-activated blasts. In addition, increased incorporation of tritiated thymidine into PHA-activated blast cells is also induced by supernatants from two-way mixed leucocyte cultures. The data show that even at the evolutionary level of teleost fish, amplifying/regulatory leucocyte products exist. It is suggested that these factors play as important a role in the regulation of the immune response in fish as they do in mammals.