Comparison of two formulations of oxytetracycline given prophylactically to reduce the incidence of bovine respiratory disease in feedlot calves

A trial involving 1,803 feedlot calves was conducted under commercial feedlot conditions in western Canada to compare the relative effectiveness of a new oxytetracycline formulation, administered either intramuscularly (BMI) or subcutaneously (BMS), to a currently available oxytetracycline formulation, administered intramuscularly (LAB), for the prevention of bovine respiratory disease (BRD) in feedlot calves. All experimental treatments were administered upon arrival at the feedlot and again on the third day after arrival.

Over the entire feeding period, there were no significant differences (p≥0.05) in the BRD treatment rates or the BRD relapse rates between either the BMI or BMS groups compared to the LAB group. Similarly, there were no significant differences (p≥0.05) in the BRD treatment rates in the BMI or BMS groups from days 8-14, days 15-90, or days 1-90 of the feeding period compared to the LAB group. However, during the first seven days of the feeding period the BRD treatment rate in the BMI group was 1.55 times (p<0.05) higher than in the LAB group. From days 1-90 and day 1 to the end of the feeding period, the overall mortality rates, BRD mortality rates, and BRD case fatality rates were two to six times lower in the BMS and BMI groups as compared to the LAB group; however, these differences were not statistically significant (p≥0.05).

These data indicate that both the intramuscular and subcutaneous administration of a new oxytetracycline formulation are comparable to the intramuscular administration of a currently available oxytetracycline formulation when given to calves upon arrival at the feedlot.

     

A clinical comparison of two injectable oxytetracycline preparations for the treatment of pneumonia in calves

Summary

The experiment was set up to make a clinical comparison in 140 pneumonic calves of two injectablc oxytetracycline formulations with different pharmacokinetic properties: Engcmycin^® 10% DD and Terramycin^® LA. The animals were examined clinically on the day of admission (day 0) and 1,2,3, 6 and 21 days thereafter. Calves were treated on day 0 with either Engemycin^® 10% DD (n=70) or Terramycin^® LA (n=70) at a dose of 20 mg/kg. If animals were not cured after one single injection, a second or even third injection was given at day 3 and day 6 respectively. No significant differences between the two treatment groups were found with regard to the number of injections needed for a complete cure, the evolution of dyspnoea, or the restoration of appetite. Thus both preparations gave comparable recovery rates. A difference between the two groups existed in the evolution of body temperature during the test period: the return to a normal body temperature occured more rapidly in the Engemycin^® 10% DD group. Regarding the tolerance aspects the degree of irritation depended in the preparation used. Calves treated with Engemycin^® 10% DD showed significantly less swelling of the injection site on day 1 then calves treated with Terramycin^® LA.     

Intra-articular administration of doxycycline in calves

Objective-To evaluate local tissue compatibility of doxycycline hyclate (DOX) in antebrachiocarpal joints of calves. Animals-10 healthy calves between 80 and 110 kg. Procedures-Calves were assigned to 2 treatment groups. Calves in groups DOX(low) and DOX(high) were administered 5 and 10 mg of DOX, respectively, locally in 1 antebrachiocarpal joint. The contralateral joint served as a control joint and was injected with 0.9% NaCl solution. General and local clinical findings were scored. Several variables were assessed in blood and synovial fluid for 9 days. Calves were euthanatized and pathologic changes and drug residues evaluated. Results-Throughout the study, none of the calves had clinical changes or abnormal hematologic values. Significant differences between treatment and control joints were evident only for matrix metalloproteinases at 0.5 hours after injection, with less activity for the DOX-treated joints in both treatment groups. Values for all synovial fluid variables, except nitric oxide, increased significantly during the first 12 to 72 hours after arthrocentesis in control and DOX-treated joints. Histologic examination revealed minimal infiltration of inflammatory cells independent of the treatment. No drug residues were detected 9 days after arthrocentesis in any tissues obtained from the liver, kidneys, fat, and skeletal muscles. Conclusions and Clinical Relevance-DOX had excellent intra-articular compatibility in healthy calves. Arthrocentesis induced a mild transient increase of inflammatory mediators in the synovial fluid. Significant decreases in matrix metalloproteinase activity in DOX-treated joints may indicate a potential chondroprotective effect of DOX.     

A comparison of prophylactic efficacy of tilmicosin and a new formulation of oxytetracycline in feedlot calves

Two replicated-pen field studies were performed under commercial feedlot conditions in western Canada to compare the administration of long-acting oxytetracycline at 30 mg/kg body weight (BW) versus tilmicosin at 10 mg/kg BW to feedlot calves upon arrival at the feedlot. Ten thousand nine hundred and eighty-nine, recently weaned, auction market derived, crossbred beef steer and bull calves were randomly allocated upon arrival at the feedlot to one of 2 experimental groups as follows: oxytetracycline, which received intramuscular long-acting oxytetracycline (300 mg/mL formulation) at a rate of 30 mg/kg BW; or tilmicosin, which received subcutaneous tilmicosin (300 mg/mL formulation) at a rate of 10 mg/kg BW. There were 20 pens in each experimental group. In Study 1 and in the combined analysis, the initial undifferentiated fever (UF) treatment rate was significantly (P < 0.05) higher in the oxytetracycline group as compared with the tilmicosin group. There were no significant (P > or = 0.05) differences in first UF relapse, second UF relapse, third UF relapse, overall chronicity, overall rail, overall mortality, bovine respiratory disease (BRD) mortality, hemophilosis mortality, arthritis mortality, or miscellaneous mortality rates between the experimental groups in either study or in the combined analysis. In addition, there were no significant (P > or = 0.05) differences in initial weight, final weight, weight gain, days on feed, daily dry matter intake, average daily gain, or the dry matter intake to gain ratio between the experimental groups in either study or in the combined analyses. In the economic analysis, there was a net economic advantage of $5.22 CDN per animal in the oxytetracycline group, due to a lower prophylactic cost, even though the UF therapeutic cost was higher.     

Morphologic alterations of Anaplasma marginale in calves after treatment with oxytetracycline.

The morphologic features of Anaplasma marginale were determined after treatment of infected calves with oxytetracycline. By light microscopy, anaplasma bodies in erythrocytes of treated calves were enlarged and vacuolated, small and dense, or comma shaped. Several degenerated forms of anaplasma bodies were observed by electron microscopy. There was a blending of the 2 membranes surrounding initial bodies, aggregation of nucleoprotein at the periphery of the subunit, and vacuolation. A 2nd form of degeneration was coalescence of subunits in marginal bodies. A 3rd form of degeneration was unification of subunits of anaplasma bodies and clumping of nucleoprotein. A 4th form of degeneration was the persistence of an anaplasma body as a solitary, irregularly shaped mass containing electron-opaque clumps.     

Penetration of oxytetracycline into tissue-cages in calves

Concentrations of oxytetracycline (OTC) in serum and tissue-cage fluid (TCF) from subcutaneous tissue-cages were determined after single and repeated intravenous and intramuscular doses of 10 mg/kg to calves. Intravenous administration resulted in higher levels, and greater area under curve (AUC) in TCF, than did intramuscular administration. However, the penetration measured as the ratio of AUC in TCF to AUC in serum was equal, and therefore independent of the route of administration. A linear relationship between AUC in serum and AUC in TCF could be demonstrated. Half-lives of OTC in serum were 4.9 +/- 3.1 h after intravenous, and 6.1 +/- 2.0 h after intramuscular administration. In TCF the half-lives were 21.5 +/- 4.4 h and 24.5 +/- 11.5 h after intravenous and intramuscular administration, respectively. Repeated dosing resulted in accumulation of OTC in TCF. Lesser accumulation in older cages indicated altered characteristics of the cages with the passage of time. In serum, no substantial accumulation was seen after repeated i.v. dosing until the dosing interval was shortened to 6 h.     

An evaluation of the relative efficacy of a new formulation of oxytetracycline for the treatment of undifferentiated fever in feedlot calves in western Canada

A field trial was performed under commercial feedlot conditions in western Canada to compare the efficacy of a new formulation of long-acting oxytetracycline (LA 30) to a standard long-acting oxytetracycline formulation (LA 20) and florfenicol (FLOR) for the treatment of undifferentiated fever (UF) in calves that received metaphylactic tilmicosin upon arrival at the feed-lot. Seven hundred and ninety-seven recently weaned, auction market derived, crossbred, beef calves suffering from UF were allocated to 1 of 3 experimental groups as follows: LA 30, which received intramuscular long-acting oxytetracycline (300 mg/mL formulation) at the rate of 30 mg/kg body weight (BW) at the time of allocation; LA 20, which received intramuscular long-acting oxytetracycline (200 mg/mL formulation) at the rate of 20 mg/kg BW at the time of allocation; or FLOR, which received intramuscular florfenicol administered at the rate of 20 mg/kg BW at the time of allocation and again 48 hours later. Two hundred and sixty-six animals were allocated to the LA 30 group, 265 animals were allocated to the LA 20 group, and 266 animals were allocated to the FLOR group. The relative efficacy of the LA 30 group, as compared with the LA 20 and FLOR groups, was assessed by comparing relapse, chronicity, wastage, and mortality rates. The overall mortality (RR = 0.50) rate in the LA 30 group was significantly (P < 0.05) lower than in the LA 20 group. However, the overall chronicity (RR = 2.56) and overall wastage (RR = 6.97) rates of the LA 30 group were significantly (P < 0.05) higher than in the LA 20 group. There were no significant (P > or = 0.05) differences in UF relapse rates or cause specific mortality rates between the LA 30 and LA 20 groups. In the economic analysis, there was an advantage of $28.59 CDN per animal in the LA 30 group compared with the LA 20 group. The overall chronicity (RR = 2.25) and overall wastage (RR = 2.80) rates of the LA 30 group were significantly (P < 0.05) higher than the FLOR group. There were no significant (P > or = 0.05) differences in UF relapse rates, overall mortality rates, or cause specific mortality rates between the LA 30 and FLOR groups. In the economic analysis, there was an advantage of $12.90 CDN per animal in the LA 30 group compared with the FLOR group. In summary, the results of this study indicate that it is more cost-effective to use a new formulation of long-acting oxytetracycline (300 mg/mL formulation administered at a rate of 30 mg/kg BW) than a standard long-acting oxytetracycline formulation (200 mg/mL formulation administered at a rate of 20 mg/kg BW) or florfenicol for the treatment of UF in feedlot calves that have previously received metaphylactic tilmicosin upon arrival at the feedlot.     

Disposition of oxytetracycline in pigs after i.m. administration of two long-acting formulations

Two commercially available long-acting oxytetracycline (OTC) formulations were administered by the intramuscular (i.m.) route to six healthy pigs at the recommended dose of 30 mg/kg. After 2 h the mean maximum concentration (C(max)) reached values of 8.1 +/- 2.2 and 15.4 +/- 11.1 microg/mL, respectively. These concentrations remained higher than 0.5 microg/mL for more than 5 days after drug administration. The area under the concentration time curve (AUC09 days) of each formulation was 255 +/- 76.5 and 399.2 +/- 123 microg. h/mL, respectively, and the mean residence time (MRT) was around 3 days for both formulations. No significant differences were observed between the pharmacokinetic parameters of the two formulations, showing the bioequivalence of the two formulations studied according to the criteria established by the Food and Drug Administration (FDA) and the Committee for Veterinary Medicinal Products (CVMP).     

Pharmacokinetics of oxytetracycline and therapeutic implications in veal calves

Pharmacokinetic parameters of oxytetracycline were analysed in healthy preruminant veal calves after intravenous, intramuscular and oral administration. The serum half-lives in the β-elimination phase of both 10% and 20% solutions after i.v. injection of 10 mg/kg were similar (7.07 ± 1.36 h and 7.16 ± 1.17 h, mean ± SD), whereas the total body clearance and the apparent volume of distribution were higher for the 20% solution. Serum concentrations above 0.5 μg/ml were maintained with both formulations during 12–24 h but were only above 4 μg/ml to 5 h. Intramuscular administration of the 20% solution gave a complete absorption with two rate constants of absorption, a faster (t_1/2a1= 0.27 h) and a slower one (t_1/2a2= 10.90 h) responsible for the delayed elimination half-life after this route of application (t_1/2β= 9.83 ± 1.35 h). Mean serum concentrations reached a maximum level of 3.01 ± 0.72 μg/ml at 4.01 ± 2.84 h and decreased to 0.5 μg/ml between 12 and 24 h. 50 mg/kg given orally with a milk replacer were found to have a mean bioavailability of 46.35%. A mean serum peak level of 4.99 ± 1.37 μg/ml was achieved at 9.16 ± 1.99 h and the mean concentration was still above 0.5 μg/ml after 48 h. The elimination half-life (t_1/2β= 10.66 ± 3.15 h) reflected the slow absorption step (t_1/2a2= 10.15 h) following that responsible for the initial faster absorption (t_1/2a2= 1.99 h). Comparison of the area under the serum curves gave mean values of 117% for tetracycline and of 53% for chlortetracycline relative to oxytetracycline (arbitrarily fixed at 100%) after identical oral dosage of the three tetracyclines. We also propose and discuss a dosage schedule based on minimal inhibitory concentrations of different susceptible pathogens     

Comparative efficacy of drugs in bovine anaplasmosis

Summary Calves experimentally infected withAnaplasma marginale were subjected to chemotherapeutic treatment in groups, each group receiving one drug only. Observations were made on clinical signs, haematological changes, parasitaemias and levels of antibodies as measured by the complement fixation test. The most effective treatment was with imidocarb; other drugs which were apparently effective were steclin, terramycin and aureomycin in that order, while chloroquin diphosphate and camoquin gave little indication of therapeutic value.

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Eficacia Comparativa De Drogas En La Anaplasmosis Bovina

Resumen Diferentes grupos de terneros infectados conAnaplasma marginale se sometieron a tratamientos quimioprofilácticos con una droga específica cada uno. Se observaron los síntomas clínicos, cambios hematológicos, parasitémias y niveles de anticuerpos, estos últimos mediante la prueba de fijación de complemento. El tratamiento más efectivo fue con imidocarb y en orden decreciente con esteclin, terramicina y aureomicina. El difosfato de cloroquin y el camoquin no tuvieron valor terapéutico.

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Efficacite Comparee De Medicaments Contre L'anaplasmose Bovine

Résumé Des veaux expérimentalement infectés parAnaplasma marginale ont été soumis à des traitements chimiothérapiques de groupe, chacun de ces groupes ne recevant qu'un seul des produits essayés. Les observations ont parté sur les signes chimiques, les variations dans les formules hématologiques, la parasitémie et le niveau des anticorps mesurés par la réaction de fixation du complément. Le traitement le plus efficace a été obtenu avec l'imidocarbamide; les autres corps qui ont été apparemment efficaces ont été: steclin, terramycine et aureomycine dans cet ordre, alors que le diphosphate deichloroquine et al camoquine n'ont paru avoir qu'une action thérapeutique très limitée.