A comparative study on irritation and residue aspects of five oxytetracycline formulations administered intramuscularly to calves, pigs and sheep

After intramuscular (IM) administration (dose 20 mg/kg) of three 20% (Terramycin/LA (product A), Alamycin LA (product B) and Terralon 20% LA (product C) and two 10% oxytetracycline (OTC) formulations (Engemycin 10% (product D) and Oxyject 10% (product E)), to calves, pigs and sheep, the OTC residue concentrations were determined in organs, muscle, fat, plasma, urine and at the injection sites at 10 days post injection (p.i.). At that time the irritation at the injection site was studied, too. The three 20%-formulations (products A, B, C) and one 10%-formulation (product E) induced considerable local irritation in and between the muscles. This was most pronounced in calves and pigs; in sheep the extent of irritation was limited. Ten days after administration of formulations A, B, C and E, OTC residues were found in organs and the OTC recovery at the injection sites varied widely among the three species. Following IM injection of product D minimal tissue irritation and no OTC residues could be detected at the injection site at 10 days p.i. The differences in local tissue irritation and the residue state of the carcass (including injection site) are related to the various solvent systems used in the formulations.     

'Pink eye' or 'zere oogjes' or keratoconjunctivitis infectiosa ovis (KIO). Clinical efficacy of a number of antimicrobial therapies

In a comparative study the clinical efficacy of five different treatments of keratoconjunctivitis infectiosa ovis (KIO) were tested, namely an intramuscular injection of chloramphenicol base (dosage 15 mg/kg), spiramycin base (Suanovil dosages 10 to 25 mg/kg), oxytetracycline (Engemycine Forte, Terramycin LA, dosages respectively 5 and 10 mg/kg), tiamulin (Dynamutulin, dosage 10 mg/kg) and subcutaneous injection of procaine penicillin G, benzathine penicillin G. and dihydrostreptomycin in the lower eyelid. It appeared from these field trials that spiramycin base, oxytetracycline and tiamulin had a clearly positive effect on the clinical course of 'pink eye', although with tiamulin there was only a temporary effect (high percentage of relapses). In view of the field data the following dosage schemes are, for the time being, advised: spiramycin base (Suanovil), and oxytetracycline (formulation with a good biological availability) both 20 to 30 mg/kg and, if necessary, to be repeated on days 5 and 10 after the first intramuscular injection. The dosage scheme advised for tiamulin is 20-30 mg/kg to be repeated on day 3 and if necessary on days 6 and 9 after the intramuscular injection. In mild cases it is sufficient to rub the eyes with for example oxytetracycline eye-ointment, a few times a day.     

Bioequivalence Study of Two Long-acting Oxytetracycline Formulations in Sheep

Two commercially available long-acting oxytetracycline hydrochloride formulations (Primamycin LA (Pfizer) and Terralent 20% LA (İ.E. Ulagay)) were administered by the intramuscular route to 20 clinically healthy sheep at a dose of 20 mg/kg. The study was performed in a two-period crossover design. Plasma samples were analysed by high-pressure liquid chromatography. The mean maximum concentrations (C _max) was 8.00 ± 2.05 μg/mland 8.61 ± 1.42 μg/ml, respectively. The mean area under the concentration time curve (AUC) values were 154.95 ± 50.37(μg h)/ml and 161.70 ± 47.02(μg h)/ml, respectively. The 90%confidence intervals for the ratio of C _max and AUC values for the test and reference product are with in the interval 70−143% for C _max and interval 80-−125% for AUC proposed by EMEA. It was concluded that Primamycin LA and Terralent 20% LA formulations are bioequivalent in their rate and extent of drug absorbtion. Ozdemir N. and Yıldırım, M., 2006. Bioequivalence study of two long-acting oxytetracycline formulations in sheep. Veterinary Research Communications, 30(8), 929–934     

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 and residues in milk of oxytetracyclines administered parenterally to dairy goats

OBJECTIVE: To determine for two commercial preparations of oxytetracycline (OTC) the pharmacokinetic behaviour, the presence of detectable milk residues and the penetration in milk of OTC administered by intravenous (IV) (conventional formulation [CF]) and intramuscular (IM) routes (CF and long-acting [LA] formulations) in goats producing milk. The effects of these formulations on plasma activity values of creatine kinase (CK) and lactate dehydrogenase (LDH) were also determined as indicators of tissue damage. PROCEDURE: Five healthy lactating goats producing 1.5+/-0.5 L/d milk and weighing 56.0+/-4.8 kg were used. Single doses of OTC chlorhydrate (CF) were administered (20 mg OTC/kg) by IV (Trial 1 IV) and IM (Trial 1 IM) routes and OTC dehydrate (LA) by the IM route. The same goats were first given IV CF, then IM CF followed by IM LA with 3 weeks between each treatment. Blood and milk samples were taken. The quantification of OTC was performed by HPLC and the plasma activities of CK and LDH enzymes were determined by spectrophotometry. The presence of OTC residues in milk was determined by a commercial reagent. The plasma pharmacokinetic parameters were calculated using a two-compartment model. RESULTS: Estimates of kinetic variables following IV administration were: Vss= 400.0+/-120.0 mL/kg and CL= 110.0+/-14.0 (mL/h)/kg. The t(fi) for IV= 3.0+/-0.3 h; IM, CF = 10.5+/-2.1 h and IM, LA = 15.1+/-3.1 h. The concentration of OTC in milk at 48 h was: IV= 0.6+/-0.4; IM CF= 1.1+/-0.2 and at 72 h (IM LA)= 0.6+/-0.1 microg/mL and the penetration in milk of OTC was: IV= 70.0+/-18.0; IM CF= 79.0+/-14.0 and IM LA= 66.0+/-6.0%. The areas under the curve of CK and LDH activities in plasma were calculated by the trapezoidal method. Values of CK and LDH IM, LA were greater (P < 0.05) than those observed for IM, CF at 2 and 3 days after administration of the antibiotic. Finally, the bioavailability of OTC CF = 92.0+/-22.0 and LA= 78.0+/-23.0% was suitable for its usage by the IM route in lactating goats. CONCLUSION: Plasma concentration-time values of OTC administered parenterally in production dairy goats showed similar bioavailability for the two pharmaceutical preaprations. The presence of detectable residues in milk indicates that milk should not be used for human consumption for 2 and 3 days after administration of conventional and long-acting formulations, respectively. The increments in CK and LDH activities after the IM administration of LA are consistent with the presence of tissue damage provoked by the pharmaceutical preparations at the injection site.     

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.     

五种土霉素注射液在猪体内的药物代谢动力学比较研究

对五种土霉素注射液产品(A、B、C、D和得米先20%)进行了猪体内的药代动力学比较研究。五组猪分别按20 mg/kg的剂量耳后肌肉注射,HPLC测定血药浓度,3P97软件拟合血药浓度-时间数据,计算药代动力学参数。五种长效土霉素注射液均符合二室开放模型,峰浓度值分别为1.511、.772、.132、.022、.72μg/mL,AUC分别为48.456、0.22、52.41、66.045、9.8(μg.h)/mL。比较而言,得米先20%药动学最好,其次为产品C,产品B最差。     

Immunisation against East Coast fever by the infection and treatment method: evaluation of the use of ice baths for field delivery and appraisal of an acid formulation of long-acting tetracycline

Immunisation by the infection and treatment method using the Katete strain is currently the most efficient prophylactic technique to control East Coast fever (ECF) in the endemic areas of the Eastern Province of Zambia. The maintenance of the cold chain in liquid nitrogen up to the time of inoculation and the cost of the reference long-acting oxytetracycline (Terramycin LA, Pfizer) are the main drawbacks of the method. The work presented in this paper aims at reducing the cost of immunisation against ECF by using an ice bath for the field delivery and a cheaper long-acting oxytetracycline formulation as chemotherapeutic agent. In experimental conditions, the results from 40 calves immunised after various periods of storage on ice ranging from 4 to 32 h indicate that deferred immunisation performed with a stabilate kept on ice for up to 6h after thawing has an efficiency of 90%. Moreover, sporozoites kept on ice were still surviving 32 h after thawing. In a field trial, 91 calves were inoculated with a stabilate kept for 3.5-5.5 h after thawing and dilution whereas 86 calves were immunised using the standard method. Clinical and parasitological reactions to immunisation were monitored as well as the seroconversion. In the field trial, the deferred immunisation was more efficient than the standard method. The acid formulation of oxytetracycline that was tested was found as suitable as the reference alkaline formulation for the chemotherapeutic control of the Katete strain in ECF immunisation. One indoor trial was carried out on 10 animals and a field trial involved 93 calves.     

Observations of a long-acting formulation of oxytetracycline in red deer (Cervus elaphus)

Six nine-month-old red deer were injected intramuscularly with a long-acting injectable solution of oxytetracycline (Terramycin-LA, Pfizer Ltd) at a dose rate of 20 mg/kg. Four similar control deer were injected with saline. There was no significant pain response to injection, and only minor palpable swellings at the injection site were observed in three oxytetracycline-treated and one control animal. No statistically significant changes in white blood cell numbers, blood fibrinogen, creatine phosphokinase or glutamic oxaloacetic transaminase concentrations occurred as a result of oxytetracycline administration up to seven days after injection. Mean plasma oxytetracycline concentration reached a peak (4.68 mg/l) two hours after injection and declined to levels below assay sensitivity (0.3 mg/l) in five deer 72 hours after injection, and in all deer by 96 hours after injection. No gross lesions at the injection site were observed at slaughter 30 days after injection. There were traces of oxytetracycline at the injection site muscle of two deer after 30 days, but residues were not detected in injection site muscle from the other four deer, or in any of the liver, kidney or other muscle specimens.     

Penetration of some antibiotics into the lacrimal fluid of sheep

Antibiotic concentrations were determined in the lacrimal fluid of sheep following subcutaneous application of penicillin/ dihydrostreptomycin into the lower eyelid, and intramuscular administration of spiramycin base, tiamulin, and oxytetracycline formulations. The penetration of penicillin and dihydrostreptomycin into the lacrimal fluid was poor. The spiramycin and tiamulin concentrations in the lacrimal fluid were 10‐ and 4‐fold higher than in the serum. The peak spiramycin concentration in the lacrimal fluid was 3.4 ±0.8 μg/ml at 8 h post injection (p.i.) and the drug could be detected at least 72 h p. i. For tiamulin and oxytetracycline (OTC) peak concentrations of 1.53 ±0.70 and 1.88 ±1.9 μg/ml, respectively, were achieved in the lacrimal fluid and these drugs could be detected 25 to 30 h p.i. The OTC and tiamulin concentration‐time curves for lacrimal fluid and serum were parallel, whereas for the spiramycin appearance in the lacrimal fluid was delayed.     

Influence of the injection site on the pharmacokinetics of amoxicillin after intramuscular administration of a conventional and a long-acting formulation in sheep

The pharmacokinetics of amoxicillin (AMX) were investigated in sheep following intravenous (i.v.) and intramuscular (i.m) injection, comparing two different drug formulations, a conventional and a long-acting AMX-trihydrate suspension. For the i.m. application two different injections sites, the neck area and the hind limb were used to identify possible differences in the kinetic parameters related to the site of injection. A three-compartment open model could best describe AMX disposition after i.v. administration. Data analysis after i.m. administration of the conventional suspension at both injection sites revealed the occurrence of a flip-flop phenomenon, clearly indicating that absorption of AMX is the rate-limiting step of its overall disposition. A moderate effect of the injection site was observed with a tendency for the neck area to be advantageous, mainly in terms of rate rather than extent of absorption. Injection of the long-acting formulation led to a focal depot formation, thus yielding lower but remarkably prolonged serum AMX levels reflected in the respective terminal half-lives. The concentration–time profile of AMX after administration of the long-acting formulation was less affected by the injection site, but the low serum levels justify its use only in cases in which a high susceptibility of the involved bacterial population is confirmed.     

Comparison of pharmacokinetic parameters for two oxytetracycline preparations in pigs

Pharmacokinetics of oxytetracycline (OTC) were studied in 10 pigs after administration of 20 mg/kg body weight of either a conventional (OTC-C) or a long-acting (OTC-LA) preparation.
After intravenous administration of OTC-C the elimination half-life for OTC was 3.75 h, with approximately 75% of the dose being excreted in the urine in 1 week. Intramuscular (i.m.) injection of OTC-C resulted in plasma peak values after 4 h, while OTC-LA after i.m. administration produced the highest plasma levels within 1 h, although these were lower than with OTC-C.
For both preparations the bioavailability after i.m. administration was 95–100% and about 70% of the dose was excreted in the urine during the first week.
With OTC-C given i.m., plasma concentrations above 0.5 μg/ml were maintained for 28 h and with OTC-LA for 35 h indicating a weak retard effect of the latter.
Pronounced tissue damage at the injection site was seen 1 and 2 weeks after the administration of OTC-LA, while OTC-C produced very little irritation. OTC could be found at the injection site for 2 weeks, the concentrations being higher for OTC-LA than for OTC-C.     

The effect of two different oxytetracycline treatments in experimental Ehrlichia phagocytophila infected lambs

The effect of 2 different oxytetracycline treatments in acute E. phagocytophila infected lambs was investigated. Twenty 5-month-old lambs of the Dala and Rygja breeds were used. Ten lambs were inoculated intravenously with a stabilate of an ovine E. phagocytophila strain. On the third day of fever, 4 lambs were given long-acting oxytetracycline (Terramycin prolongatum vet, Pfizer) (20 mg/kg) intramuscularly and another 4 lambs were given short-acting oxytetracycline (Terramycin vet, Pfizer) (10 mg/kg) intravenously for 5 consecutive days. The lambs were examined for the presence of Ehrlichia infection by blood smear evaluation, polymerase chain reaction (PCR) and antibody titre against E. equi. One month after the last antibiotic treatment, 250 ml citrate blood from each of these lambs were inoculated into each of 10 susceptible lambs, which were observed during the following 6 weeks. The results indicate that oxytetracycline given in the acute stage of the infection may effectively terminate the development of fever, rickettsemia and weight reduction in E. phagocytophila infected lambs. No difference was observed between the 2 treatment groups. However, at least 3 of 8 antibiotic treated lambs (37.5%) were still infected with granulocytic Ehrlichia 3 months after treatment.     

Residues from long-acting antimicrobial preparations in injection sites in cattle

Objective To investigate tissue residues of two longacting oxytetracycline (OTC) preparations in cattle.
Design A randomised drug residue trial.  

Animals

Two hundred and forty beef cattle in 24 groups of ten.
Procedure Two blind-coded 200 mg/mL OTC preparations were used in five treatment regimens of various combinations of injection sites (from one to five) and administrations (one or two). Five cattle from each group were slaughtered at 21, 30 and 60 days after injection and the injection site, urine, kidney and diaphragm muscle analysed for residues.
Results The OTC concentration exceeded the maximum residue limit in kidney in animals slaughtered 21 days after treatment, which is the prescribed withholding period. Concentration at the injection site was much greater than the maximum residue limit 30 days post-treatment, but not 45 days post-treatment. The residue was smaller when OTC had been injected in multiple sites. There was no difference between the two OTC preparations.
Conclusion A review of the maximum injection volume, site of injection and the withholding period is needed for long-acting OTC formulations.     

Irritation, bioavailability, and residue aspects of ten oxytetracycline formulations administered intramuscularly to pigs

After intramuscular administration to pigs (dosage 20-35 mg/kg) great differences were found among 10 injectable oxytetracycline (OTC) formulations with respect to irritation and persistence at the injection site and to the residue state of edible tissues. The OTC recovery percentages at the injection site 7-10 days after injection ranged from less than 0.001 to 0.15 per cent for three 10 per cent-formulations and from 0.12 to 20.5 per cent for seven 20 per cent-formulations. The OTC recovery percentage was obvious related to the extent of tissue irritation at the injection site, which was particularly evident for the 20 per cent-formulations. Serious doubt is expressed about advantages of so-called 'long-acting' formulations.     

Bioavailability of amoxycillin in pigs

Amoxycillin was administered to pigs intravenously (i.v.), intramuscularly (i.m.) and orally (p.o.), in a cross-over design to examine the bioavailability ( F ) of various drug formulations. These included: a sodium salt for reconstitution in water and administration i.v.; trihydrate salt in an oil base for intramuscular administration producing 'conventional' duration of plasma concentrations; a trihydrate salt in oil base giving prolonged (LA) duration, and a trihydrate powder for oral administration in solution. The concentration of amoxycillin in plasma was measured by high-performance liquid chromatography, and its pharmacokinetic variables were assessed for the individual pigs by use of non-compartmental methods.
  Following i.v. administration (8.6 mg/kg), amoxycillin was eliminated rapidly with a mean residence time ( MRT ) of 1.4 h. After i.m. administration of the conventional formulation (14.7 mg/kg), the plasma amoxycillin concentration peaked at 2 h at 5.1 μg/mL. The bioavailability was 0.83. Intramuscular administration (14.1 mg/kg) of the long acting formulation (i.m. LA), lead to two peaks in plasma at 1.3 and 6.6 h. The bioavailability was calculated to be 1.11. After p.o. administration to fasted pigs, peak concentration was reached after 1.9 h, and the bioavailability was 0.33. In fed pigs, the corresponding values were 3.6 h and 0.28. Data showed that treatment of respiratory tract diseases in pigs by p.o. dosing alone, may not be optimal, because of the relatively low bioavailability and the fact that infections often result in reduced feed and water consumption. A rational treatment regime for susceptible respiratory pathogens includes an initial i.m. injection, followed by p.o. dosing every 12 h. Alternatively, the long acting formulation may be administered i.m. in a dose of 15 mg/kg, which would lead to active plasma concentrations for approximately 48 h.     

Some features of the antibody response of sheep

Six nine-month-old red deer were injected intramuscularly with a long-acting injectable solution of oxytetracycline (“Terramycin-LA”, Pfizer Ltd) at a dose rate of 20 mg/kg. Four similar control deer were injected with saline. There was no significant pain response to injection, and only minor palpable swellings at the injection site were observed in three oxytetracycline-treated and one control animal. No statistically significant changes in white blood cell numbers, blood fibrinogen, creatine Phosphokinase or glutamic oxaloacetic transaminase concentrations occurred as a result of Oxytetracycline administration up to seven days after injection. Mean plasma Oxytetracycline concentration reached a peak (4.68 mg/1) two hours after injection and declined to levels below assay sensitivity (0.3 mg/1) in five deer 72 hours after injection, and in all deer by 96 hours after injection. No gross lesions at the injection site were observed at slaughter 30 days after injection. There were traces of Oxytetracycline at the injection site muscle of two deer after 30 days, but residues were not detected in injection site muscle from the other four deer, or in any of the liver, kidney or other muscle specimens.     

‘Pink eye’ or ‘zere oogjes’ or Keratoconjunctivitis Infectiosa Ovis (KIO)

In a comparative study the clinical efficacy of five different treatments of keratoconjunctivitis infectiosa ovis (KIO) were tested, namely an intramuscular injection of chloramphenicol base (dosage 15 mg/kg), spiramycin base (Suanovil^® dosages 10 to 25 mg/kg), oxytetracycline (Engemycine^® Forte, Terramycin^® LA, dosages respectively 5 and 10 mg/kg), tiamulin (Dynamutulin^®, dosage 10 mg/kg) and subcutaneous injection of procaine penicillin G, benzathine penicillin G, and dihydrostreptomycin in the lower eyelid.

It appeared from these field trials that spiramycin base, oxytetracycline and tiamulin had a clearly positive effect on the clinical course of ‘pink eye’, although with tiamulin there was only a temporary effect (high percentage of relapses).

In view of the field data the following dosage schemes are, for the time being, advised: spiramycin. base (Suanovil^®), and oxytetracycline (formulation with a good biological availability) both 20 to 30 mg/kg and, if necessary, to be repeated on days 5 and 10 after the first intramuscular injection. The dosage scheme advised for tiamulin is 20–30 mg/kg to be repeated on day 3 and if necessary on days 6 and 9 after the intramuscular injection. In mild cases it is sufficient to rub the eyes with for example oxytetracycline eye‐ointment, a few times a day.     

Comparative pharmacokinetics,bioavailability and renal clearance of five parenteral oxytetracycline‐20% formulations in dairy cows

Summary

Oxytetracycline (OTC) concentrations in plasma and milk of dairy cows were determined following a single intramuscular injection of five oxytetracycline‐20% formulations at a dosage of approximately 10 mg/kg. For obtaining pharmacokinetic reference parameters, one 10% OTC formulation was administered intravenously. The five 20% formulations were compared and evaluated pharmacokinetically with respect to absorption rate, peak plasma and milk OTC concentrations, biological half‐life, and relative bioavailability. The mean maximum plasma OTC concentrations varied between 4.5 and 6.8 μg/ml and were achieved between 5 and 10 h p.i., depending on the formulation involved. The mean maximum milk concentrations, ranging from 1.12 to 1.92 μg/ml, were achieved 12 to 24 h p.i. A plasma OTC concentration exceeding 0.5 μg/ml was maintained for 48 h to 70 h, and in milk for 33 to 49 h, depending on the formulation involved.

Formulations exhibiting the lowest clinically noticeable irritation showed the highest peak plasma OTC concentrations and the best bioavailability. Among the formulations the calculated withholding periods for milk were in the range of 3 to 4 days and for edible tissues of 9 to 14 days. The OTC and creatinine clearances were significantly correlated to each other and to the urinary flow. OTC was excreted predominantly by glomerular filtration, partly by tubular secretion minus urogenital (distal renal tubuli and bladder) reabsorption.     

Comparative pharmacokinetics and bioavailability of eight parenteral oxytetracycline‐10% formulations in dairy cows

Summary

In plasma and milk the oxytetracycline (OTC) concentrations were determined following a single intramuscular administration of eight 10%‐formulations to dairy cows at a dose of approximately 5 mg/kg. Two of these formulations were injected intravenously to obtain reference values of the drug's pharmacokinetic parameters. The eight formulations were compared and evaluated pharmacokinetically with respect to absorption rate, peak plasma and milk OTC concentrations, biological half‐life, and relative bioavailability. The mean maximum plasma OTC concentrations, ranging from 2.0 to 4. 1 μg/ml, were achieved between 4 and 12 hours post injection, depending on the formulation involved. The mean maximum milk OTC concentrations, in the range between 0.92 and 1.43 μg/ml, were achieved 12 to 24 h p. i. The OTC milk concentration‐time profile ran parallel to the OTC plasma concentration‐time profile.

After intravenous administration the time for the appearance of OTC in milk was shorter (1–2 hours p.i.), the peak milk OTC concentration was higher (1.7–1.9 μg/ml) and achieved earlier (6–8 h p.i.). and the OTC persistence in milk shorter than after i.m. administration. Formulations exhibiting the lowest clinically noticeable irritation showed the most favourable pharmacokinetic characteristics: rapid absorption with the highest peak plasma OTC concentrations and good bioavailability.

The plasma and milk protein binding for OTC was respectively 71.7± 7.4% and 84.8 ± 5.45%. Withdrawal times for milk and edible tissues are presented on the basis of preset tolerance or detection limits.