Pharmacokinetic and tissue distribution study of oxytetracycline in rainbow trout following bolus intravenous administration.

Oxytetracycline pharmacokinetics and tissue distribution were studied in rainbow trout following bolus i.v. administration at 5 mg/kg. The mean serum (log) drug concentration data were plotted against time (linear). The decay curve was described by a three-component exponential decay function and a three-compartment model. The t1/2 of rapid distribution was 0.9 h, the t1/2 of the slow distribution was 5.9 h and the t1/2 elimination was 81.5 h. Clearance was 25.4 ml/kg/h and Vd(area) 2988 ml/kg. Regression analysis of the serum levels for the three intervals, 0.5-2.0 h, 6.0-18.0 h, and 24-96 h, indicated that the rates of decay for each interval were 0.6151 h-1, 0.0564 h-1 and 0.0088 h-1 respectively. Rates of equilibration between tissues and serum were determined. Kidney equilibrated the fastest with t1/2 to equilibration of 1.1 h for H (anterior) kidney and 1.98 h for P (posterior) kidney. The highest drug levels were found in the liver and the lowest were in the brain.

The effect of temperature and starvation on the clearance of bacteria from the bloodstream of rainbow trout (Salmo gairdneri Richardson).

The blood clearance of 51Cr-labeled heat-killed Salmonella pullorum was generally biphasic and exponential for each phase. Starvation had little significant effect on this pattern, although the rate of first phase clearance was probably slower. Raising the water temperature from 8 degrees C to 18 degrees C enhanced the rate of clearance of the second phase to almost exactly double that at 8 degrees C. At 18 hr postinoculation, the spleen contained much more radioactivity per gm than any other tissue. This finding is in marked contrast to earlier work that showed that at 1 hr postinoculation, the kidney contained the most, and it suggests that redistribution of bacteria occurred. The most distinct effect of temperature stress on tissue localization of bacteria was in the heart: A rising temperature stress caused increased numbers of bacteria to localize within the heart. Less clear-cut changes were also seen in other tissues with different treatments. With the possible exception of starvation effecting a slower first phase clearance rate, we have been unable to demonstrate that the vascular clearance mechanisms, including the reticuloendothelial system, are significantly compromised by raising the water temperature or by starvation.

The quantitative clearance of bacteria from the bloodstream of rainbow trout (Salmo gairdneri).

The blood clearance of 51Cr-labelled heat-killed Salmonella pullorum was biphasic and exponential for each phase. This pattern was the same for all three concentrations of bacteria used. The initial more rapid phase lasted for approximately 15 minutes when roughly 90% of the bacteria had been cleared. The second slower phase started 25 to 30 minutes post-inoculation and lasted for approximately 25 to 30 minutes. The tissue distribution of bacteria showed that in both absolute and relative terms, the kidney was the most important organ, accounting for more than 70% uptake of the bacteria. These kinetics demonstrate that rainbow trout at 8 degrees C are able to clear their bloodstream of Salmonella very efficiently, in a fashion very similar to mammals. It is not know, however, which of the various possible clearance mechanisms dominates each phase.

Distribution of neomycin in bull calves after intramuscular injection.

Neomycin sulfate was injected intramuscularly in calves. Blood and tissue samples were taken at zero, one, two, four, six, eight and 24 hours after administration. The tissues with high levels (greater than 10 mug/g) of drug at the one hour period were kidney cortex and medulla, urine, blood serum and the injection site. By 24 hours after administration only the kidney cortex and urine had high levels of neomycin. The drug could not be detected in any brain tissues and very small amounts (less than 1 mug/g) were present in the bile, thymus and vitreous humor. Levels greater than 5 mug/g were present in lung tissues for less than four hours but were greater than 2 mug/g for more than 24 hours.The mean level in the injection site was greater than 700 mug/g at one hour but only trace amounts were found at 24 hours.On the basis of the tissue drug concentration intramuscularly administered neomycin was suggested as therapeutically useful for respiratory and urinary tract infections caused by susceptible bacteria.

A study of drug residues in milk following intrauterine infusion of antibacterial drugs in lactating cows.

Intrauterine infusion of nine antibacterial compounds caused detectable drug residues in 17 out of 165 cows or in 25 out of 1110 posttreatment milkings. Four cows treated with pyrolidinomethyl tetracycline suspension had drug residues at the first milking. One cow had residues after oxytetracycline treatment, two after procaine penicillin G, three after acriflavin and after chloramphenicol-dapsone and four after hibitane. Nitrofurazone, nitrofurathiazide and Hibitane Compound(R) did not cause detectable inhibitory residues in any milk sample.

A simple, reliable and inexpensive method for the collection of rat urine.

Aluminum foil attached to the bottom of hanging-type rat cages approximately 10 cm from the front of the cage was used for collecting rat urine. Most urine samples were obtained within 1 hour of placing the rat in the cage.

The kinetics of hematopoiesis in the light horse II. The hematological response to hemorrhagic anemia.

Hemorrhagic anemia was experimentally produced in three Standardbred horses by removing approximately 63% of the red cell mass and the accompanying plasma during a three day interval. Red cell parameters were examined daily for 45 days and then weekly until termination of the experiment 250 days after production of the anemia. Leukocytes, platelets and bone marrow aspirates were examined at regular intervals for 25 days after the final phlebotomy. At 24 hours after the last bleeding, 75-selenomethionine was injected intravenously to measure the lifespan of the newly produced erythrocytes. The erythrocyte lifespan was found to be 139 days as compared to the 155 day erythrocyte lifespan for three normal standardbred horses measured previously by similar techniques. The maximum decrease in erythrocyte numbers occurred four, two and two days following the last phlebotomy to 43, 39 and 44% of the original values. The prebleeding erythrocyte levels were regained at approximately 63, 91 and 98 days respectively. During the initial 45 days post phlebotomy the maximum increase in mean cell colume was 2, 4 and 7 mj-3 respectively. During the recovery period there was erythrocyte production of 6.84, 6.99, and 6.12 x 10-9 cells/kg/day. At the same time the absolute production of hemoglobin was 44.6, 50.0, and 51.0/gm/day or on a relative basis 0.096, 0.114 and 0.113 gm/kg/day.

The kinetics of hematopoiesis in the light horse III. The hematological response to hemolytic anemia.

The hematological response to acetylphenylhydrazine hemolytic anemia was studied in three standardbred horses. The lifespan of erythrocytes produced during the most severe phase of the anemia were measured with 75-selenomethionine and found to be 144 days as compared to the 139 day lifespan in response to hemorrhagic anemia or 155 days in normal standardbred horses measured previously using the same technique. The erythrocyte counts returned to initial values in 42 days (37, 34 and 54 days) a mean erythrocyte production of 6.4 times 10-12 erythrocytes/day. The mean hemoglobin production was 0.31 gm/kg body weight/day as compared to 0.11 gm Hb/kg/day previously observed in response to hemorrhagic anemia. The mean increase in erythrocyte mean cell volume was 12 mu-3 during the acute response phase to hemolytic anemia in contrast to the absence of a significant increase in the mean cell volume as previously observed during response to hemorrhagic anemia. Free Heinz bodies separated from erythrocytes during the acute phase could not be differentiated from platelets on the hemocytometer counting chamber with standard techniques.