Efficacy of intramuscular treatment of beef cows with oxytetracycline to reduce mastitis and to increase calf growth

Spring-calving multiparous Angus x Hereford cows were used to determine the efficacy of intramuscular treatment with oxytetracycline to reduce the incidence of mastitis-causing bacteria, decrease milk somatic cell counts (SCC), and increase calf growth. During 2 yr, milk samples were collected from each quarter from a total of 319 cows at 8 to 14 d after calving and at weaning, to determine the presence of bacteria and SCC. A California mastitis test (CMT) was performed on milk from each quarter of each cow at the initial sample collection. Cows with a CMT score of 1, 2, or 3 in at least one quarter, were randomly assigned to receive either an intramuscular injection of oxytetracycline (n = 63) or the control vehicle (n = 60), and cows with a CMT score of 0 or trace in all four quarters were not treated (n = 196). Calf weights were determined at birth, early lactation, and weaning. The number of somatic cells in milk and the percentage of quarters that were infected increased as CMT score increased (P < 0.01). The presence of mastitis-causing bacteria at calving increased (P < 0.05) the incidence of infection at weaning. The presence of mastitis-causing bacteria at weaning was associated with increased SCC for quarters and average SCC for cows (P < 0.01). Average SCC per cow at weaning increased (P < 0.05) as the number of infected quarters per cow increased. Treatment did not alter (P > 0.10) the percentage of cows or quarters infected with mastitis-causing bacteria or SCC of cows or quarters at weaning. Average SCC per cow was negatively correlated (P < 0.05) with calf weights at early lactation, but not with weaning weights of calves. Treatment did not influence (P > 0.10) calf weights at early lactation or at weaning. Cows with one or more dry quarters after calving had calves that weighed less at early lactation and weaning than cows with four functional quarters (P < 0.01). Intramuscular oxytetracycline treatment of beef cows that had CMT scores of 1 or greater after calving did not reduce intramammary infection rates or increase calf weights at weaning.     

Pharmacokinetics and renal clearance of oxytetracycline after intravenous and intramuscular administration to dairy cows

Summary

Following intravenous administration of an oxytetracycline‐HC 1 and an oxytetracycline‐dihydrate formulation to dairy cows, no statistical difference could be found between the pharmacokinetic parameters, derived from the three‐compartment model, of these preparations. Urinary recovery was continued for a period of 72 h following intravenous or intramuscular OTC administration.

The recovery of OTC in the urine in the 72‐h period was in the range of 73% to 96% of the available dose administered.

The renal OTC clearance, the renal creatinine clearance, the urinary flow, and the interrelationships of these were determined on the basis of urine and plasma data. The mean OTC renal clearance ranged from 482 to 1050 ml/min and the creatinine clearance from 651 to 1304 ml/min. The OTC and creatinine clearances were significantly correlated to the urine flow up to 30 ml/min. The total body clearance and renal clearance values were of the same order of magnitude, and along with the urine recovery data they provided evidence of predominantly renal route of OTC elimination in dairy cows. The renal OTC elimination is the net result of mainly glomerular filtration, partly tubular secretion, minus reabsorption in the urogenital tract.     

Pharmacokinetics and renal clearance of oxytetracycline after intravenous and intramuscular administration to dairy cows

Following intravenous administration of an oxytetracycline-HC1 and an oxytetracycline-dihydrate formulation to dairy cows, no statistical difference could be found between the pharmacokinetic parameters, derived from the three-compartment model, of these preparations. Urinary recovery was continued for a period of 72 h following intravenous or intramuscular OTC administration. The recovery of OTC in the urine in the 72-h period was in the range of 73% to 96% of the available dose administered. The renal OTC clearance, the renal creatinine clearance, the urinary flow, and the interrelationships of these were determined on the basis of urine and plasma data. The mean OTC renal clearance ranged from 482 to 1050 ml/min and the creatinine clearance from 651 to 1304 ml/min. The OTC and creatinine clearances were significantly correlated to the urine flow up to 30 ml/min. The total body clearance and renal clearance values were of the same order of magnitude, and along with the urine recovery data they provided evidence of predominantly renal route of OTC elimination in dairy cows. The renal OTC elimination is the net result of mainly glomerular filtration, partly tubular secretion, minus reabsorption in the urogenital tract.     

Subclinical mastitis of beef cows

Two beef cow herds were investigated to determine the prevalence of subclinical mastitis and to determine whether it contributed to decreased weaning weight of calves nursed by affected cows. Quarter samples obtained about 30 days after calving were evaluated by the California mastitis test and by direct microscopic cell count. In 1 herd, a 92-cow confinement operation, 17 quarters of 12 cows were infected with Staphylococcus aureus, Streptococcus sp other than agalactiae, or Klebsiella sp. Mean 205-day adjusted weights were 203.9 kg and 218.2 kg for calves nursed by infected vs noninfected cows. In the other herd, a 75-cow range-pasture operation, 8 quarters of 8 cows were infected, all with S aureus. Mean 205-day adjusted weights were 162.5 kg and 174.6 kg for calves nursed by infected vs noninfected cows.     

Correlation between oral fluid and plasma oxytetracycline concentrations after intramuscular administration in pigs

The penetration of oxytetracycline (OTC) into the oral fluid and plasma of pigs and correlation between oral fluid and plasma were evaluated after a single intramuscular (i.m.) dose of 20 mg/kg body weight of long‐acting formulation. The OTC was detectable both in oral fluid and plasma from 1 hr up to 21 day after drug administration. The maximum concentrations (C_max) of drug with values of 4021 ± 836 ng/ml in oral fluid and 4447 ± 735 ng/ml in plasma were reached (T_max) at 2 and 1 hr after drug administration respectively. The area under concentration–time curve (AUC), mean residence time (MRT) and the elimination half‐life (t_1/2β) were, respectively, 75613 ng × hr/ml, 62.8 hr and 117 hr in oral fluid and 115314 ng × hr/ml, 31.4 hr and 59.2 hr in plasma. The OTC concentrations were remained higher in plasma for 48 hr. After this time, OTC reached greater level in oral fluid. The strong correlation (r = .92) between oral fluid and plasma OTC concentrations was observed. Concentrations of OTC were within the therapeutic levels for most sensitive micro‐organism in pigs (above MIC values) for 48 hr after drug administration, both in the plasma and in oral fluid.     

Tissue residue depletion of oxytetracycline after repeated intramuscular administration of Oxysentin 100 in sheep

The depletion profile of oxytetracycline was studied in healthy sheep after intramuscular administration of Oxysentin 100, given at a dose of 10 mg oxytetracycline per kg body weight once daily for 5 consecutive days. Five medicated sheep were slaughtered at 0, 2, 4, 6, 9 and 12 days postmedication, and injection site, muscle, fat, liver and kidney tissues were sampled and analysed using a liquid chromatographic method, which was fully validated for oxytetracycline and 4-epi-oxytetracycline. At day 0 postmedication, the concentrations of oxytetracycline marker residue (sum of oxytetracycline and 4-epi-oxytetracycline) in all tissues examined were at the mg/kg level. At day 2 postmedication, the concentrations of oxytetracycline marker residue in all injection site and kidney samples examined were higher than the corresponding maximum residue limits (MRLs) established by the European Union, while the concentrations in muscle and liver tissues of two and three out of five animals examined, respectively, were below the corresponding MRLs. At days 4 and 6 postmedication, concentrations of oxytetracycline marker residue above the MRLs were found only in the injection site, whereas at day 9 postmedication, all observations were below the corresponding MRLs.     

Florfenicol pharmacokinetics in lactating cows after intravenous, intramuscular and intramammary administration

Pharmacokinetics of florfenicol 30% injectable solution was determined in lactating cows after intravenous, intramammary and intramuscular administration. Serum concentration-time data generated in the present study were analysed by non-compartmental methods based on statistical moment theory. Florfenicol half-life was 176 min, mean residence time 129 min, volume of distribution at steady-state 0.35 L/kg, and total body clearance 2.7 mL/min·kg after intravenous administration at 20 mg/kg. The absorption after intramuscular administration appeared slow and the kinetic parameters and the serum concentration vs. time curve were characteristic of absorption rate-dependent elimination. The absorption after intramammary administration of florfenicol at 20 mg/kg was good (53.9%) and resulted in serum concentrations with apparent clinical significance. The intramammary administration resulted in serum florfenicol concentrations that were significantly higher than the respective serum concentrations following Intravenous administration 4 h after administration and thereafter. Florfenicol absorption was faster from the mammary gland than from the muscle. The maximum serum concentrations ( C _max) were 6.9 μg/mL at 360 min after intramammary administration and 2.3 μg/mL at 180 min after intramuscular administration. The bioavailability of florfenicol was 54% and 38% after intramammary and intramuscular administration, respectively. The C _max in milk was 5.4 μg/mL at 180 min after intravenous and 1.6 μg/mL at 600 min after intramuscular administration.     

Pharmacokinetics of spiramycin after intravenous, intramuscular and subcutaneous administration in lactating cows

Spiramycin is a macrolide antibiotic that is active against most of the microorganisms isolated from the milk of mastitic cows. This work investigated the disposition of spiramycin in plasma and milk after intravenous, intramuscular and subcutaneous administration. Twelve healthy cows were given a single injection of spiramycin at a dose of 30,000 IU/kg by each route. Plasma and milk were collected post injection. Spiramycin concentration in the plasma was determined by a high performance liquid chromatography method, and in the milk by a microbiological method. The mean residence time after intravenous administration was significantly longer (P less than 0.01) in the milk (20.7 +/- 2.7 h) than in plasma (4.0 +/- 1.6 h). An average milk-to-plasma ratio of 36.5 +/- 15 was calculated from the area concentration-time curves. Several pharmacokinetic parameters were examined to determine the bioequivalence of the two extravascular routes. The dose fraction adsorbed after intramuscular or subcutaneous administration was almost 100% and was bioequivalent for the extravascular routes, but the rates of absorption, the maximal concentrations and the time to obtain them differed significantly between the two routes. Spiramycin quantities excreted in milk did not differ between the two extravascular routes but the latter were not bioequivalent for maximal concentration in the milk. However, the two routes were bio-equivalent for the duration of time the milk concentration exceeded the minimal inhibitory concentration (MIC) of various pathogens causing infections in the mammary gland.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of oxytetracycline after intramuscular administration with lidocaine in sheep, comparison with a conventional formulation

The pharmacokinetic behaviour of oxytetracycline (OTC) was studied in 11 sheep after intravenous and intramuscular administration at a single dosage of 20 mg kg⁻¹ bodyweight. A conventional formulation was injected by the intravenous route and two different preparations were administered by the intramuscular route: a conventional formulation (T-100) and an aqueous solution of OTC with lidocaine (1 per cent) (OTC-Q. The objective was to determine whether there are differences between both formulations in the disposition kinetics of OTC after intramuscular administration to sheep. After intravenous administration of the conventional formulation, plasma oxytetracycline concentrations were best fitted to an open two-compartment model. Mean apparent volume of distribution was 0·77±0·02 litre kg⁻¹ and the harmonic mean half-life was three hours. The OTC transfer process between central and peripheral compartments was fast and that did not influence the elimination process. After intramuscular administrations of both formulations, half-lives were longer than after intravenous administration (mean values of 14·1 and 58·2 hours for T-100 and OTC-L respectively). In both cases, a biphasic absorption, a ‘flip-flop’ model and a complete bioavailability were found. OTC-L provided therapeutic plasma concentrations over 0·5 μg ml⁻¹ (the minimum inhibitory concentration for most susceptible pathogens) for a longer period of time than T-100 (72 hours compared with 36 or 48 hours).     

Pharmacokinetics and bioavailability of carbetocin after intravenous and intramuscular administration in cows and gilts

The pharmacokinetics of carbetocin, which is used to control postpartum hemorrhage after giving birth, was studied in cows and gilts after a single intravenous (IV) or intramuscular (IM) injection. Blood samples from animals were assessed by oxytocin radioimmunoassay, and then the pharmacokinetic parameters were calculated using a noncompartmental model. For gilts, there was no significant difference between half-life (T_1/2λZ), mean residue time (MRT), and maximum concentration (C_max) between IM and IV administration. Conversely, the time to reach the C_max (T_max) and MRT were higher following administration of 350 μg/animal in cows via the IM administration compared with IV. The longest T_1/2λZ was 0.85 hr, indicating carbetocin was absorbed and eliminated rapidly in both animal species after administration. The T_max was similar between cows and gilts following IM administration. Moreover, the C_max after IM injection was about half that of IV administration in both animals. The bioavailability was more than 80% in cows, suggesting administration via the IM route is efficient. This is in agreement with the longer T_1/2λZ in cows after IM administration. However, the IV route is recommended for gilts due to a lower bioavailability (35%) and shorter T_1/2λZ after IM administration compared with IV.     

Cortisol and luteinizing hormone after adrenocorticotropic hormone administration to postpartum beef cows

Cortisol and luteinizing hormone (LH) were measured in serum after the administration of adrenocorticotropic hormone (ACTH) to suckled (S) and nonsuckled (NS) beef cows. Blood was sampled on 2 consecutive days every 2 weeks for four bleeding periods starting 14 days after calving. Cows were injected with 200 IU ACTH or saline in a 2-day switchback design. Serum was collected before ACTH or saline injection and at 30-min intervals thereafter for 8 hours. Average cortisol concentrations in serum were similar in S and NS cows (6.4 +/- .6 and 6.1 +/- .8 ng/ml, respectively) after saline. Average cortisol concentrations in serum collected during an 8-hr period after ACTH on days 14, 28, 42 and 56 postpartum were 24.7 +/- 2.4, 31.8 +/- 3.5, 36.4 +/- 4.2 and 40.7 +/- .5 ng/ml, respectively, for S cows, and 31.1 +/- 2.9, 44.7 +/- 5.2, 45.0 +/- 5.7 and 46.0 +/- 5.4 ng/ml, respectively, for NS cows. Cortisol response to ACTH, measured as area under the response curve, was greater (P less than .05) in NS than in S cows. Amount of cortisol released by 200 IU ACTH was maximal by days 28 to 29 postpartum in NS cows, but the response increased gradually between days 14 to 15 and days 56 to 57 in S cows. overall, LH in serum averaged .55 +/- .08 ng/ml for S cows and .92 +/- .06 ng/ml for NS cows after saline, and .49 +/- .07 ng/ml for S cows and .94 +/- .06 ng/ml for NS cows after ACth. Although mean and peak serum LH concentrations did not differ between cows given ACTH and those given saline, the number of LH peaks and the number of cows having LH after saline. Mean serum LH concentrations were lower (P less than. 05) in S than in NS cows at 28 days postpartum. The number of LH peaks was lower (P less than .05) and the magnitude of the largest LH peak tended to be lower (P less than .06) in S cows at all sampling periods.     

Penetration of oxytetracycline into the nasal secretions and relationship between nasal secretions and plasma oxytetracycline concentrations after oral and intramuscular administration in healthy pigs

Bimazubute, M., Cambier, C., Baert, K., Vanbelle, S., Chiap, P., Gustin, P. Penetration of oxytetracycline into the nasal secretions and relationship between nasal secretions and plasma oxytetracycline concentrations after oral and intramuscular administration in healthy pigs. J. vet. Pharmacol. Therap. 34 , 176–183. The penetration of oxytetracycline (OTC) in plasma and nasal secretions of healthy pigs was evaluated during the first study, in response to oral dose of 20 mg of OTC per kg of body weight (bwt) per day as a 400 mg/kg feed medication (n = 5) and to intramuscular (i.m.)‐administered formulations at 10 mg/kg bwt (n = 5), 20 mg/kg bwt (n = 5), 40 mg/kg bwt (n = 5). Concentrations of OTC in plasma and nasal secretions were determined by a validated ultra‐high performance liquid chromatography associated to tandem mass spectrometry method (UPLC/MS/MS). The objectives were to select the efficacy treatment and to evaluate the possibility to predict nasal secretions concentrations from those determined in plasma. The animals were housed together in each experiment. In each group, the treatment was administered once daily during 6 consecutive days, and nasal secretions and plasma were collected after 4 and 24 h at day 2 and day 6. For oral administration, only one medicated feed was prepared and distributed to all the animals together and was consumed in approximately 1 h. To meet recommendations of efficacy for OTC in nasal secretions, only the i.m. of 40 mg/kg bwt associated to an inter‐dosing interval of 24 h provides and maintains concentrations in nasal secretions ≥1 μg/mL, appropriate to the MIC 50 and 90 of Pasteurella multocida and Bordetella bronchiseptica, respectively, the main pathological strains in nasal secretions. It has been demonstrated that, using a generalized linear mixed model (GLMM), OTC in the nasal secretions (μg/mL) can be predicted taking into account the OTC concentrations in plasma (μg/mL), according to the following equation: OTC_{nasal secretions} = 0.28 OTC_plasma?1.49. In a second study, the pharmacokinetic behaviour of OTC in plasma and nasal secretions of healthy pigs was investigated, after single‐dose i.m. of 40 mg/kg bwt of the drug. Blood samples and nasal secretions were collected at predetermined times after drug administration. The data collected in 10 pigs for OTC were subjected to non‐compartmental analysis. In plasma, the maximum concentration of drug (C_max), the time at which this maximum concentration of drug (T_max) was reached, the elimination half‐life (t½) and the area under the concentration vs. time curve (AUC) were, respectively, 19.4 μg/mL, 4.0, 5.1 h and 150 μg·h/mL. In nasal secretions, C_max, T_max, t½ and AUC were, respectively, 6.29 μg/mL, 4.0, 6.6 h and 51.1 μg·h/mL.     

Pharmacokinetics of chloramphenicol in cows after intramuscular application

The concentrations of chloramphenicol and its water-soluble metabolites in the plasma of six clinically healthy heifers were measured at intervals during five days after intramuscular administration of free chloramphenicol (20 mg/kg) in a vehicle containing 40% of an organic solvent. Estimations were carried out by a colorimetric method and by high pressure liquid chromatography (for the very low values beyond the second day).For free chloramphenicol a peak concentration of 1.7 g/ml at 7.3 h after injection was found (MIC: 5 g/ml). Bioavailability was calculated to be 63%.It is shown that absorption was apparently not a uniform process but occurred rather slowly (t_1/2(ab)=10.2 h) for the main part of the available dose, whereas one sixth was quickly absorbed (t_1/2(ab)=0.7 h). The apparent half-time of elimination was 10.2 h for the unchanged drug. At the fifth day after administration the plasma concentration was below the limit of detectability (10 ng/ml) in all animals.     

Pharmacokinetics of benzydamine in dairy cows following intravenous or intramuscular administration

Five lactating cows were given benzydamine hydrochloride by rapid intravenous (0.45 mg/kg) and by intramuscular (0.45 and 1.2 mg/kg) injection in a crossover design. The bioavailability, pharmacokinetic parameters and excretion in milk of benzydamine were evaluated. After intravenous administration, the disposition kinetics of benzydamine was best described using a two-compartment open model. Drug disposition and elimination were fast (t _1/2: 11.13±3.76 min;t _1/2: 71.98±24.75 min; MRT 70.69±11.97 min). Benzydamine was widely distributed in the body fluids and tissues (V _d(area): 3.549±1.301 L/kg) and characterized by a high value for body clearance (33.00±5.54 ml/kg per min). After intramuscular administration the serum concentration-time curves fitted a one-compartment open model. Following a dose of 0.45 mg/kg, theC _max value was 38.13±4.2 ng/ml at at _max of 67.13±4.00 min; MAT and MRT were 207.33±22.64 min and 278.01±12.22 min, respectively. Benzydamine bioavailability was very high (92.07%±7.08%). An increased intramuscular dose (1.2 mg/kg) resulted in longer serum persistence (MRT 420.34±86.39 min) of the drug, which was also detectable in milk samples collected from both the first and second milking after treatment.Abbreviations HPLC high-pressure liquid chromatography - IC50 concentration to inhibit the activity of an organism by 50% - IM intramuscular(ly) - IV intravenous(ly) - NSAID non-steroidal antiinflammatory drugs - pK _a negative logarithm of the ionization constant (K _a) of a drug; other abbreviations are listed in footnotes to tables     

Evaluation of systemic administration of gentamicin for treatment of coliform mastitis in cows

Recovery of cows (n = 61) with mastitis caused by gram-negative bacteria and treated systemically with an antibiotic (gentamicin) to which the bacteria were susceptible in vitro, was compared with recovery of cows (n = 13) with similar infections treated with a systemically administered antibiotic (erythromycin) to which the bacteria were resistant in vitro or with recovery of cows (n = 12) not given an antibiotic systemically. In the first part of the study, cows were selected for treatment groups by use of a diagnostic scheme designed to predict whether the mastitis was caused by gram-negative or gram-positive bacteria. In the second part of the study, all cows were treated without systemic administration of an antibiotic. Significant difference was not observed in the outcome of the disease between cows given gentamicin and cows of the other 2 treatment groups at 24 hours or at 4 weeks after treatment. At 24 hours after initial treatment, 71.9% of cows treated with gentamicin, 92.3% of those treated with erythromycin, and 45.5% not treated systemically had improved appetite. At 4 weeks after initial treatment, of the cows treated with gentamicin, 11.5% died; in 32.8%, lactation ceased in the affected mammary gland; in 21.3%, lactation was decreased in the affected gland; and 34.4% returned to normal lactation and health. Of cows treated with erythromycin, none died; in 23%, lactation ceased in the affected mammary gland; in 23%, lactation decreased in the affected gland; and 54% returned to normal lactation and health.(ABSTRACT TRUNCATED AT 250 WORDS)     

Local tissue damage in cows after intramuscular administration of preparations containing phenylbutazone, flunixin, ketoprofen and metamizole

Tissue irritation after intramuscular injections of 4 nonsteroidal anti-inflammatory agents was studied in 5 lactating cows. Preparations containing phenylbutazone, flunixin, metamizole (dipyrone) and ketoprofen were investigated; physiological saline was used as a control substance. Tissue reactions at the injection sites were examined by palpation and by determining serum creatine kinase. A kinetic method based on creatine kinase released from the injured muscle tissue was used, which allowed estimation of the amount of damaged muscle. The metamizole preparation clearly provoked signs of pain all the cows. After flunixin and phenylbutazone injections slight reactions were observed, and ketoprofen and saline did not cause any clinical signs. Some palpatory findings after injections were found for all the preparations except saline. Based on serum creatine kinase, the 2 most irritating preparations were the ones containing flunixin and phenylbutazone. After injections of these 2 substances, the estimated amount of damaged muscle was about 80 grams. The statistical difference between flunixin and phenylbutazone and the other 2 preparations was significant. Physiological saline had no effect on serum creatine kinase. For preparations containing phenylbutazone and flunixin, intravenous administration is recommended.     

Pharmacokinetics and residual behaviour in milk of oxytetracycline in cows following administration of uterine pessaries

The plasma kinetics and residual depletion in milk of cows treated by the intrauterine route with pessaries containing oxytetracycline (OTC) were evaluated. The antibiotic was administered to five healthy Friesian cows at a dosage of 3g/head in the early post partum phase. Blood samples were collected before and at different time intervals (3, 6, 12, 24, 48, 72, 84, and 96 h) after treatment. Milk was drawn before treatment and at 12-h intervals for 4 consecutive days. Samples were analysed by a high-performance liquid chromatography method and the pharmacokinetic parameters were processed using the minimum Akaike information criterion estimation (MAICE) test. The mean values obtained indicated a relatively low area under the concentration time curve (25.19+/-12.61 microg/mg per h) and maximum plasma concentration (Cmax) (0.549+/-0.278 microg/mL) with delayed time to Cmax (11.71+/-4.15 h) and elimination half-life (21.96+/-4.42 h). A similar pattern could be shown for milk, in which measurable residual levels are found in two out of five animals until the 72nd hour after treatment. Data obtained demonstrate that OTC administered as a solid form is poorly and slowly absorbed from the uterus of cows.