A single-dose pharmacokinetic study of oxolinic acid and vetoquinol, an oxolinic acid ester, in cod, Gadus morhua L., held in sea water at 8 degrees C and in vitro antibacterial activity of oxolinic acid against Vibrio anguillarum strains isolated from diseased cod.

The pharmacokinetic properties of the antibacterial agent oxolinic acid and vetoquinol, the carbitol ester of oxolinic acid, were studied after intravenous (i.v.) and oral (p.o.) administration to 100-150 g cod, Gadus morhua L., held in sea water at 8 degrees C. Following i.v. injection, the plasma drug concentration-time profile showed two distinct phases. The distribution half-life (t1/2alpha) was estimated at 1.3 h, the elimination half-life (t1/2beta) as 84 h and the total body clearance (Cl(T)) as 0.047 L kg(-1) h(-1). The volume of distribution at steady state, Vd(ss) was calculated to be 5.5 L kg(-1), indicating good tissue penetration of oxolinic acid in cod. Following p.o. administration of oxolinic acid or vetoquinol, the peak plasma concentrations (C(max)) of oxolinic acid and the time to peak plasma concentrations (T(max) were estimated to be 1.2 and 2.5 microg mL(-1) and 24 and 12 h, respectively. The bioavailabilities of oxolinic acid following p.o. administration of oxolinic acid and vetoquinol were calculated to be 55 and 72%, respectively. The in vitro minimum inhibitory concentration (MIC) values of oxolinic acid against three strains of Vibrio anguillarum isolated from diseased cod were 0.016 microg mL(-1) (HI-610), 0.250 microg mL(-1) (HI-618) and 0.250 microg mL(-1) (HI-A21). Based on a MIC value of 0.016 microg mmL(-1) a single p.o. administration of 25 mg kg(-1) of oxolinic acid maintains plasma levels in excess of 0.064 microg mL(-1), corresponding to four times the MIC-value, for approximately 12 days. The analogous value for a single p.o. dose of 25 mg kg(-1) of oxolinic acid administered as vetoquinol was 13 days.

The efficacy of a single intraperitoneal injection of oxolinic acid in the treatment of bacterial infections in goldsinny wrasse (Ctenolabrus rupestris) and corkwing wrasse (Symphodus melops) studied under field and laboratory conditions.

The efficacy of a single intraperitoneal injection of oxolinic acid to control an outbreak of atypical Aeromonas salmonicida infection in goldsinny wrasse (Ctenolabrus rupestris) and in the treatment of systemic vibriosis in corkwing wrasse (Symphodus melops) was examined. In addition a field study was performed to examine the effect of medication on the survival rate of goldsinny wrasse in Atlantic salmon cages. Four groups of wild caught goldsinny wrasse, each of 50 fish, were treated with an intraperitoneal injection of propylene glycol:saline (50:50) (control) or 50 mg/kg oxolinic acid at a concentration of 50 mg/mL. Three days after medication the fish in all groups were treated by an intraperitoneal injection of prednisolone acetate and an increase in seawater temperature from 9.0 to 11.5 degrees C. Cumulative mortalities were 18% in the two groups treated with oxolinic acid and 94 and 100% in the unmedicated control groups, giving a 'relative percentage survival' (RPS) value of 82%. A laboratory maintained population of originally wild caught corkwing wrasse experiencing high daily mortality was treated with oxolinic acid (50 mg/kg) or propylene glycol:saline (control). Cumulative mortalities were 84% (control) and 42% (oxolinic acid medicated group) giving an RPS value of 50%. In a field investigation using goldsinny wrasse approximately 30% were medicated with oxolinic acid (50 mg/kg) prior to stocking in cages with Atlantic salmon. In two of three cages the cumulative mortality was significantly lower (P = 0.025 and P < 0.001) in the medicated groups.

Absorption, tissue distribution and excretion of flumequine and oxolinic acid in corkwing wrasse (Symphodus melops) following a single intraperitoneal injection or bath treatment.

The pharmacokinetic properties of the antibacterial agents oxolinic acid and flumequine were studied in corkwing wrasse (Symphodus melops) after either intraperitoneal injection or bath treatment. Following intraperitoneal administration the peak plasma concentrations (Cmax) and the time to peak plasma concentrations (Tmax) were estimated to be 2.0 microg/mL and 12 h, respectively, for oxolinic acid and 2.6 microg/mL and 12 h, respectively, for flumequine. In muscle, Cmax and Tmax were estimated to 6.7 microg/g and 12 h, respectively, for oxolinic acid with corresponding values of 8.5 microg/g and 13 h, respectively, for flumequine. In liver, Cmax and Tmax were calculated to 7.0 microg/g and 12 h, respectively, for oxolinic and 12.2 microg/g and 11 h, respectively, for flumequine. Elimination half-lives (t1/2 beta) of 26, 24 and 29 h, respectively, for plasma, muscle and liver were calculated for flumequine. For oxolinic acid two distinct elimination phases were found and calculated to be 16 h (t1/2 beta) and 57 h (t1/2 gamma) in plasma, 15 and 59 h, respectively, in muscle and 20 and 72 h, respectively, in liver. Bath treatment using 150 mg/L of flumequine or 200 mg/L of oxolinic acid for 72 h resulted in flumequine concentrations of 1.0 microg/mL in plasma, 5.0 microg/g in muscle and 12.4 microg/g in liver. Corresponding values for oxolinic acid were 1.0 microg/g in plasma, 2.5 microg/g in muscle and 4.9 microg/g in liver.

Reliability of goniometric measurements and visual estimates of hip ROM in patients with osteoarthrosis.

BACKGROUND AND PURPOSE: Range of motion (ROM) measurements have been included in several hip scores evaluating the results after hip surgery. The clinical procedures of performing these measurements vary and disagreement exists about the accuracy of visual estimatess compared to goniometer measurements. The purpose of this study was to study the reliability of goniometric measurements and visual estimates of hip ROM in patients with osteoarthrosis. METHOD: Hip ROM measurements (abduction, adduction, extension, flexion and internal/external rotation) were recorded by four different teams on the same day and were repeated one week later. Teams 1, 2 and 3 consisted of physiotherapists using standardized goniometric measurements. Team 4 involved an experienced orthopaedic surgeon making the assessments from visual estimates only. Twenty-five patients (6 M, 19 F; mean age 68.5 years, range 46-76 years) with osteoarthrosis of the hip, verified both clinically and radiologically, participated in the study. RESULTS: With the exception of abduction (p = 0.03), there were no significant differences between the measurements recorded on the first and the second occasions for the same teams. The coefficient of variance was 5.5% for flexion (lowest) and 26.1% for extension (highest). Reproducibility was best for flexion. There was also high reliability when all the arcs of motion were summed up (abuction + adduction + extension + flexion + internal/external rotation). With the exception of internal rotation, there were highly significant differences between the teams when two people performed the measurements compared to the values measured by a single individual. Concordance, expressed as the standardized agreement index, between visual estimates made by one individual (the orthopaedic surgeon) and goniometric measurements made by two experienced physiotherapists, were 0.77-0.83 which indicates good agreement. CONCLUSION: The reproducibility of hip ROM measurements was highest for flexion. There was also high reliability when all the six arcs of motion were summed up. Concordance between visual estimates and goniometric measurements indicates good agreement.

Absorption, tissue distribution, metabolism and excretion of ormetoprim and sulphadimethoxine in Atlantic salmon (Salmo salar) after intravenous and oral administration of Romet.

1. Uptake, bioavailability, tissue disposition and elimination of sulphadimethoxine (SDM) and ormetoprim (OMP) were examined in Atlantic salmon (Salmo salar) following intravenous and oral administration of Romet at a dose of 5 mg OMP and 25 mg SDM kg-1 fish. 2. Plasma clearance was rapid for both drugs following a single i.v. dose, characterized by t1/2 alpha = 0.48 and 0.54h, t1/2 beta = 9.9 and 25.6h for SDM and OMP respectively with a volume of distribution (Vss) = 0.389 and 2.478 l kg-1. 3. Following oral administration, peak plasma concentrations of 1.13 and 9.99 micrograms ml-1 were achieved after 17.6 and 20.3h for OMP and SDM respectively. Bioavailabilities were 85% for OMP and 39% for SDM. 4. Oral administration revealed the highest concentration of OMP in kidney and liver whereas the highest concentrations of SDM were found in muscle and bile. 5. High concentrations of N4-acetylated SDM were found in the bile indicating significant metabolism of SDM.

Long-range changes in oxytetracycline concentration and bacterial resistance toward oxytetracycline in a fish farm sediment after medication.

Following 10 days medication with oxytetracycline, marine sediment was sampled beneath three selected cages (cages 1, 2 and 3) at a fish farm over a period of 18 mnd., in order to detect any change in the sediment oxytetracycline concentration, bacterial number and bacterial resistance towards the drug. The bulk of oxytetracycline disappeared during the first weeks, but it persisted in the sediment at lower concentrations for quite some time after the medication. Half-life (t(1/2)) of oxytetracycline in the sediment was measured as: 125, 144 and 87 days under cages 1, 2 and 3, respectively. At the end of the medication, all three sediments had greater than 100% oxytetracycline-resistant bacteria. This value dropped to 20% after 72 days and stabilised at levels of between 10 and 50%. The change in bacterial numbers, described as total and plate counts, was due to seasonal variations rather than to the medication.