Plasma concentrations of oxytetracycline in swine after administration of the drug intramuscularly and orally in feed

Four pigs were used in a 2 X 2 crossover study to determine plasma oxytetracycline (OTC) concentration and OTC pharmacokinetic variables after IM administration of 2 OTC preparations--long acting OTC and a 100-mg of OTC/ml solution (OTC-LA and OTC-100, respectively)--at a dosage of 20 mg/kg of body weight. In a second study, 3 additional pigs were given ad libitum access to feed containing pure OTC (0.55 g/kg of feed). The mean (+/- SD) peak plasma OTC concentration after OTC-LA administration was 6.0 +/- 2.2 micrograms/ml at 30 minutes; the mean peak plasma OTC concentration after OTC-100 administration was 6.7 +/- 3.4 micrograms/ml at 90 minutes. Mean plasma OTC concentration after oral OTC administration in feed peaked at 0.4 micrograms/ml 48 hours after access to OTC-medicated feed and decreased to 0.25 micrograms/ml by the end of that study. Mean plasma OTC concentration was maintained at greater than 0.5 micrograms/ml for less than 48 hours after OTC-LA administration and for less than 36 hours after OTC-100 administration. Mean plasma OTC concentration decreased to less than 0.2 micrograms/ml by 72 hours after IM administration of either product. Calculation of area under the plasma OTC concentration-time curve (AUC) did not reveal significant difference between the 2 OTC formulations. There also was not significant difference (between OTC-LA and OTC-100) in the value of the disappearance rate constant after administration of either OTC formulation. The data did not indicate significant pharmacologic advantage of OTC-LA, compared with OTC-100, when either formulation was administered IM at a dosage of 20 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics and renal clearance of oxytetracycline in piglets following intravenous and oral administration

The pharmacokinetics of oxytetracycline (OTC) in three weaned piglets was studied following three routes of administration: intravenously, orally as drench, both at a dose of 20 mg/kg, and orally as medicated (400 ppm OTC) pelleted feed administered during 3 consecutive days. Analysis of the intravenous data according to the three compartment pharmacokinetic model revealed that OTC was well distributed in the body (Vf: 1.62 l/kg), had an overall body clearance of 0.25 litre/kg/h, and the elimination half-lives were in the range between 11.6 and 17.2 hrs. The mean OTC binding to plasma proteins was 75.5 +/- 4%. Following the drench route of administration the maximum plasma OTC concentration was achieved between 1 and 5 h post application and ranged between 1.18 and 1.41 micrograms/ml. The mean maximum plasma OTC concentration during medicated feed administration was 0.20 +/- 0.06 microgram/ml, which was achieved approximately 30 hours after the onset of the administration. A steady state OTC plasma level (approximately 0.2 microgram/ml) was maintained till the end of the trial. Within 48 hours after cessation of medicated feed administration the plasma OTC levels were beneath 0.06 microgram/ml. The mean OTC bioavailabilities of the oral routes were low: after the drench route of administration 9.0 +/- 0.67%, and after medicated pelleted feed administration 3.69 +/- 0.8%. The mean OTC renal clearances of each piglet ranged between 10.1 and 13.9 ml/min/kg (based on free OTC plasma fractions). The renal OTC clearance values were urine flow dependent in all piglets and significantly correlated with the renal creatinine clearance (P less than 0.005), being 3-5 times higher than the latter. It is concluded that in piglets OTC is excreted mainly by glomerular filtration and partly by tubular secretion. The potential clinical efficacy of 400 ppm OTC as medicated feed with respect to treatment, e.g. atrophic rhinitis, is discussed.     

Antibiotic aerosolization: tissue and plasma oxytetracycline concentrations in parakeets

Oxytetracycline hydrochloride (OTC) was delivered to adult parakeets by aerosolization using a DeVilbiss model 65 ultrasonic nebulizer. Trachea, lung, and plasma concentrations were ascertained at 1, 2, 4, 6, and 8 hours postaerosolization (PA). An average of 284 ml of a solution containing 2 mg OTC/ml was aerosolized over a 1-hour period into a 0.0596 M3 chamber containing 10 parakeets. The trachea and lung concentrations were more than 10 micrograms/g at 1 and 2 hours PA, had decreased to approximately 3 micrograms/g by 4 hours PA, and were below 2 micrograms/g by 8 hours. The plasma concentration never exceeded 2.6 micrograms/ml and was at 1.6 micrograms/ml by 8 hours. This study demonstrates that it is possible to achieve therapeutic concentrations of OTC by aerosolization in lung and trachea, but treatment may need to be repeated every 4-6 hours. Since the plasma concentration never reached high levels, aerosolization under the conditions of this study is not an effective way to treat systemic infections outside the respiratory tract.     

Estimation of urine flow rate in mares

To determine the rate of urine flow and thus urinary excretion in the horse from untimed urine samples alone, the flow rate, creatinine concentration, osmolarity, and refractive index of 228 quantitatively collected urine samples were determined in 53 experiments on 12 healthy Thoroughbred mares. Forty samples were collected after water-induced diuresis; 11 samples were collected after furosemide-induced diuresis. Flow rates, which ranged from 1.2 to 84.5 ml/min, could be predicted from the urinary creatinine concentration. Correlation of urinary flow with urinary creatinine concentration accounted for 94% of the variability in the urinary flow rates. Phenylbutazone was administered before collection of 168 urine samples. Urine flow rates that were predicted from urinary creatinine concentration were used to estimate phenylbutazone excretion. Urine flow could be estimated without quantitative urine collection.     

Phenylbutazone and its metabolites in plasma and urine of thoroughbred horses: population distributions and effects of urinary pH

A survey of plasma and urinary concentrations of phenylbutazone and its metabolites in thoroughbred horses racing in Kentucky was carried out. Post-race blood samples from more than 200 horses running at Latonia Racetrack and Keeneland in the Spring of 1983 were analysed. The modal plasma concentration of phenylbutazone was between 1 and 2 micrograms/ml, the mean concentration was 3.5 micrograms/ml and the range was up to 15 micrograms/ml. Oxyphenbutazone had a modal plasma concentration between 1 and 2 micrograms/ml, a mean concentration of 2.07 micrograms/ml and a range of up to 13 micrograms/ml. gamma OH-phenylbutazone had a modal plasma concentration of less than 1 microgram/ml, a mean level of 1.39 micrograms/ml and a range of up to 7.32 micrograms/ml. All plasma concentration frequency distributions were well fitted by log normal distributions. Urinary concentrations of phenylbutazone yielded modal concentrations of less than 1 microgram/ml, a mean urinary concentration of 2.9 micrograms/ml, with a range of up to 30.5 micrograms/ml. This population fitted a log-normal distribution. For oxyphenbutazone the modal concentration was less than 3 micrograms/ml, the mean concentration was 15.26 micrograms/ml, with a range to 81.5 micrograms/ml. The frequency distribution of these samples was apparently bimodal. For gamma OH-phenylbutazone, the modal concentration was less than 4 micrograms/ml, the mean concentration 21.23 micrograms/ml, with a range of up to 122 micrograms/ml. The population frequency distribution for gamma OH-phenylbutazone was indeterminate. Analysis of the pH of these post-race urine samples showed a bimodal frequency distribution. The pH values observed ranged from 4.9 to 8.7, with peaks at about pH 5.25 and 7.25. This bimodal pattern of urinary pH values is consistent with observations made in England and Japan. Urinary pH influenced the concentrations of phenylbutazone, oxyphenbutazone and gamma OH-phenylbutazone found in the urine samples. The concentration of these metabolites found in alkaline urines were from 32 to 225 times greater than those found in acidic urines. Plasma concentrations of phenylbutazone and its metabolites, however, were unaffected by urinary pH. In interlaboratory experiments, horses running at Hollywood Park were dosed with phenylbutazone at about 2 g/1000 lbs 24 and 48 h before racing, and a mean dose of 0.6 g/1000 lbs at 72 h prior to racing. Post-race plasma samples from these horses showed phenylbutazone concentrations ranging from 0.44 to 9.97 micrograms/ml, with a mean concentration of 4.09 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetics and local tolerance of a long-acting oxytetracycline formulation in camels.

Disposition and local tolerance of a new oxytetracycline (OTC) long-acting formulation were evaluated in camels by measuring the dynamics of creatine kinase. Six camels (Camelus dromedarius) were administered OTC by IV and IM routes according to a 2-period cross-over, study design. Serum OTC concentration was measured, using a microbiological assay procedure. After IV administration (5 mg/kg of body weight), mean residence time was 7.7 +/- 2.8 hours, steady-state volume distribution was 706.1 +/- 168.6 ml.kg-1 and serum clearance was 75.3 +/- 23.2 ml.kg-1.h-1. After IM administration of the long-acting OTC formulation (10 mg/kg), maximal OTC concentration (3.49 +/- 0.44 micrograms.ml-1) was observed after 7.3 +/- 3.5 hours; the mean systemic availability was near 100%, and serum concentration greater than 0.5 micrograms.ml-1 was maintained for about 72 hours. After IM administration, mean control serum activity of creatine kinase was multiplied by a factor of 3.36 +/- 1.55; at 72 hours after OTC administration, the serum creatine kinase activity returned to control values. It was concluded that OTC is an antibiotic of potential interest in camels and that a dosage regimen of 10 mg.kg-1 deserves attention when using a long-acting formulation that has good local tolerance and near total systemic availability.     

Evaluation of the effect of cephalexin and enrofloxacin on clinical laboratory measurements of urine glucose in dogs

OBJECTIVE: To determine the effects of cephalexin and enrofloxacin on results of 4 commercially available urine glucose tests in dogs. ANIMALS: 6 healthy adult female dogs. PROCEDURE: In a crossover design, cephalexin (22 and 44 mg/kg [10 and 20 mg/lb], p.o., q 8 h) or enrofloxacin (5 and 10 mg/kg [2.3 and 4.5 mg/lb], p.o., q 12 h) was administered to dogs for 1 day. Urine samples were tested for glucose at 0, 6, and 24 hours after drug administration. In vitro, dextrose was added to pooled glucose-negative canine urine samples containing either no antimicrobial or known concentrations of either antimicrobial; urine samples were then tested for glucose. RESULTS: In vivo, false-positive results were obtained by use of a tablet test in the presence of both antimicrobials and by use of a strip test in the presence of cephalexin. In vitro, false-positive results were obtained with the tablet test at the highest urine concentration of cephalexin (2,400 microg/mL) and with a strip test at the highest concentration of enrofloxacin (600 microg/mL). Enrofloxacin in urine samples containing dextrose caused the urine glucose tests to underestimate urine glucose concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Cephalexin and enrofloxacin at dosages used in clinical practice may result in false-positive or false-negative urine glucose results, and care should be taken when using urine as a basis for identifying or monitoring diabetic animals.     

Comparative pharmacokinetics of oxytetracycline in rainbow trout (Salmo gairdneri) and African catfish (Clarias gariepinus)

A comparative pharmacokinetic study was conducted in rainbow trout (Salmo gairdneri) and African catfish (Clarias gariepinus) following intravenous (i.v.) and intramuscular (i.m.) administration of oxytetracycline (OTC) at a dose rate of 60 mg/kg body weight. Trout and catfish were kept in aerated tap water in tanks at constant temperatures of 12 degrees C and 25 degrees C, respectively. The two- and three-compartment open models adequately described plasma drug disposition in African catfish and rainbow trout respectively, following i.v. OTC administration. Compared to catfish (COP = 86 +/- 10 micrograms/ml) an eightfold higher extrapolated zero time concentration was obtained in trout (COP = 753 +/- 290 micrograms/ml). A significant difference was observed with respect to the relatively large apparent distribution volumes (Vd(area] after i.v. OTC administration (trout, mean value: 2.1 l/kg; catfish, mean value: 1.3 l/kg). The mean final elimination half-lives of both fish species were greater than previously reported in mammals (trout, 89.5 h; catfish, 80.3 h). A mean maximum plasma concentration (Cmax = 56.9 micrograms/ml) was obtained in trout at 4 h after i.m. administration of OTC. In catfish a lower Cmax of 43.4 micrograms/ml was determined at about 7 h. No significant difference was observed with respect to bioavailability following i.m. administration of OTC (trout, 85%; catfish, 86%).     

Pharmacokinetics of oxytetracycline hydrochloride in rabbits

Pharmacokinetics of oxytetracycline HCl (OTC) was studied in rabbits. After 10 mg of OTC/kg of body weight was administered IV, the distribution half-life was 0.06 hour, terminal half-life was 1.32 hours, volume of distribution area was 0.861 L/kg, and total body clearance was 0.434 L/kg/h. After 10 mg of OTC/kg was given IM, the absorption half-life was 2.09 hours, extent of absorption was 71.4%, and total body clearance of the absorbed fraction was 0.576 L/kg/h. Based on these kinetic data, a dosage of 15 mg of OTC/kg, every 8 hours was developed. This dose given IM for 7 consecutive days resulted in observed steady-state maximum and minimum concentrations (mean +/- SD) of 4.7 +/- 0.3 micrograms/ml and 3.2 +/- 0.6 micrograms/ml, respectively. Twice this dose (30 mg of OTC/kg, every 8 hours) given IM caused anorexia and diarrhea.     

Pharmacokinetics and renal clearance of oxytetracycline in piglets following intravenous and oral administration

Summary

The pharmacokinetics of oxytetracycline (OTC) in three weaned piglets was studied following three routes of administration: intravenously, orally as drench, both at a dose of 20 mg/kg, and orally as medicated (400 ppm OTC) pelleted feed administered during 3 consecutive days. Analysis of the intravenous data according to the three compartment pharmacokinetic model revealed that OTC was well distributed in the body (Vie 1.621/kg), had an overall body clearance of 0.25 litre/kg/h, and the elimination half‐lives were in the range between 11.6 and 17.2 hrs.

The mean OTC binding to plasma proteins was 75.5 ± 4%. Following the drench route of administration the maximum plasma OTC concentration was achieved between 1 and 5 h post application and ranged between 1.18 and 1.41 μg/ml. The mean maximum plasma OTC concentration during medicated feed administration was 0.20 ± 0.06 μg/ml, which was achieved approximately 30 hours after the onset of the administration. A steady state OTC plasma level (approximately 0.2 μg/ml) was maintained till the end of the trial. Within 48 hours after cessation of medicated feed administration the plasma OTC levels were beneath 0.06 μg/ml. The mean OTC bioavailabilities of the oral routes were low: after the drench route of administration 9.0 ± 0.67%, and after medicated pelleted feed administration 3.69 ± 0.8%.

The mean OTC renal clearances of each piglet ranged between 10.1 and 13.9 ml/min/kg (based on free OTC plasma fractions). The renal OTC clearance values were urine flow dependent in all piglets and significantly correlated with the renal creatinine clearance (P< 0.005), being 3–5 times higher than the latter. It is concluded that in piglets OTC is excreted mainly by glomerular filtration and partly by tubular secretion. The potential clinical efficacy of 400 ppm OTC as medicated feed with respect to treatment, e.g. atrophic rhinitis, is discussed.     

Pharmacokinetics of probenecid in sheep

Six Merino ewes were given 1 g (27 g/kg) probenecid by the intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) routes. After i.v. injection, the biological half-life was 1.55 h and apparent volume of distribution at the steady state (Vdss) 0.18 l/kg. Body clearance (ClB) and renal clearance (ClR) were 0.12 l/h/kg and 0.03 l/h/kg, respectively. Approximately 28% of unchanged probenecid was excreted in urine. Plasma probenecid concentrations after i.v., i.m. and s.c. injections were 133, 37, and 31 micrograms/ml, respectively, at 15 min; 76, 36, and 34 micrograms/ml at 1 h; and 43, 23 and 34 micrograms/ml at 2 h. The average bioavailability of probenecid given by i.m. and s.c. injection was 46% and 34%, respectively. However, after 2 h, probenecid plasma concentrations remained higher when it was given subcutaneously than when it was given intramuscularly. Urine output was correlated positively (P less than 0.05) with kel and ClB. Urine pH increased significantly (P less than 0.01) for the first 2 h, and then steadily declined over the subsequent 6 h. The results suggested that probenecid in sheep was rapidly eliminated because it was rapidly excreted in the normal but alkaline urine. Subcutaneous administration of probenecid in animals may be a useful alternative to oral or i.v. administration.     

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.     

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.     

Influence of urine pH on accurate urinary protein determination in Sprague-Dawley rats

BACKGROUND: Rat urinary protein concentration is commonly measured during safety assessment studies to evaluate potential drug-induced nephrotoxicity. It has been reported that impregnated reagent test strips (dipsticks) can yield false-positive urinary protein results for alkaline urine samples. OBJECTIVE: The objective of this study was to determine if urinary dipsticks accurately assess protein concentrations, especially in alkaline rat urine. METHODS: Ten male Sprague-Dawley rats were treated with 2% sodium bicarbonate and 2% ammonium chloride to alkalinize and acidify the urine, respectively. Urine pH was measured in treated and control rats using a pH meter and urinary dipsticks with the Clinitek 500. Quantitative urinary protein results were compared to urinary dipstick protein evaluations obtained with the Clinitek 500 and sulfosalicylic acid precipitation test methods. RESULTS: The urinary dipstick pH measurement had a very high correlation (r = .98) with the pH meter technique. Samples with alkaline pH (>or=7.5) analyzed for protein by dipstick analysis were in complete agreement 34.7% of the time with the quantitative technique, which was very similar to the 39.3% agreement for samples with neutral and acidic pH (相似文献   

Pharmacokinetics of oxytetracycline in the turkey: evaluation of biliary and urinary excretion

Oxytetracycline (OTC) pharmacokinetic values in plasma and bile were ascertained after IV administration of the drug. At 6 hours after administration of 1 mg of OTC/kg of body weight, 2.15% of the dose was found in the bile and 37.6% was found in the urine. At 2 hours after administration, the peak bile-to-plasma OTC concentration ratio was 60:1. Bioavailability of OTC was 47.6% when it was administered orally to fasted turkeys and was 9.4% when administered to fed turkeys.     

Oxytetracycline pharmacokinetics, tissue depletion, and toxicity after administration of a long-acting preparation at double the label dosage

Oxytetracycline (OTC) concentration in plasma and tissues, plasma pharmacokinetics, depletion from tissue, and toxicity were studied in 30 healthy calves after IM administration of a long-acting OTC preparation (40 mg/kg of body weight) at double the label dosage (20 mg/kg). Plasma OTC concentration increased rapidly after drug administration, and by 2 hours, mean (+/- SD) values were 7.4 +/- 2.6 micrograms/ml, Peak plasma OTC concentration was 9.6 +/- 2.6 micrograms/ml, and the time to peak plasma concentration was 7.6 +/- 4.0 hours. Plasma OTC concentration decreased slowly for 168 hours (elimination phase) after drug administration, and the elimination half-life was 23.9 hours. Plasma OTC concentration exceeded 3.8 micrograms/ml at 48 hours after drug administration. From 168 to 240 hours after drug administration, plasma OTC concentration decreased at a slower rate than that seen during the elimination phase. This slower phase was termed the depletion phase, and the depletion half-life was 280.7 hours. Tissue OTC concentration was highest in kidneys and liver. Lung OTC concentration exceeded 4.4 micrograms/g of tissue and 2.0 micrograms/g of tissue at 12 and 48 hours after drug administration, respectively. The drug persisted the longest in kidneys and liver. At 42 days after drug administration, 0.1 micrograms of OTC/g of kidney was detected. At 49 days after drug administration, all OTC tissue concentrations were below the detectable limit. Reactions and toxicosis after drug administration were limited to an anaphylaxis-like reaction (n = 1) and injection site swellings (n = 2).     

Randomized efficacy trials of long-acting oxytetracycline in neonatal pigs

Prophylactic efficacy of 100 mg of long-acting oxytetracycline (OTC) given IM to neonatal pigs within 12 hours of birth was evaluated in a swine herd. The herd had a history of increased neonatal mortality, diarrhea, foot abscess, and arthritis in nursing pigs. Two trials were conducted in which liters and individual pigs were the treatment groups of interest. In both trials, OTC treatment failed to reduce mortality, diarrhea, or arthritis or the need for subsequent antimicrobial therapy (P greater than 0.05). Preweaning weight gains were not increased (P greater than 0.05) in treated pigs. However, in the individual pig trial, foot abscess rates were significantly (P = 0.01) lower in treated pigs (3.7%) than in nontreated pigs (8%). Aerobic bacteria isolated from pigs with diarrhea, arthritis, or foot abscess had minimum inhibitory concentrations for OTC greater than or equal to 64 micrograms/ml or were classed as resistant on the basis of disk-diffusion tests.     

Plasma levels of oxytetracycline, doxycycline, and minocycline in pigs after oral administration in feed.

Steady-state plasma levels were determined for oxytetracycline (OTC), doxycycline (DC), and minocycline (MC) after medication with different in-feed concentrations. Each concentration of the three tetracyclines was examined in six pigs. The animals were housed in individual pens and fed twice daily with an interval of 12 h. All pigs consumed their feed within 1 h after it was provided. Concentrations of 400, 800, 1,600, and 2,400 mg of OTC per kilogram of feed induced steady-state plasma levels ranging from .13 to .22, .19 to .50, .39 to 1.43, and 1.41 to 2.14 micrograms/ml, respectively. On a feed intake basis, pigs received 13, 26, 54 to 81, and 108 mg of OTC per kilogram of BW per day, respectively. Steady-state plasma levels after medication with 200, 400, and 800 mg of DC or MC per kilogram of feed ranged from .37 to .89, .71 to 1.14, and 1.62 to 3.18 micrograms/ml for DC and from .21 to .60, .43 to 1.05, and 1.19 to 2.62 micrograms/ml for MC. Pigs consumed 7, 13, and 26 mg of DC and 9, 18, and 36 mg of MC per kilogram of BW per day, respectively. For all three tetracyclines there was an increase in steady-state plasma levels when concentrations in feed or per kilogram of BW increased. Plasma levels were determined with both a HPLC method and a microbiological method. A good correlation existed between the results obtained by both methods. It was concluded that based on plasma levels and known in vitro activity DC and MC could be good alternatives for OTC to treat respiratory tract infections in pigs.     

Pharmacokinetics of a long-acting oxytetracycline preparation in ring-necked pheasants, great horned owls, and Amazon parrots

After a single IV or IM dose of a long-acting oxytetracycline (OTC) preparation, serum concentrations were determined at various times in the ring-necked pheasant, great horned owl, and Amazon parrot. Pharmacokinetic parameters, including serum half-life (t1/2) and apparent volume of distribution (Vd) were calculated from the OTC concentration-time curves for each species and route of administration. Significant differences (P less than 0.05) were found in the t1/2 and Vd parameters between species and routes of administration. Dosage regimens to maintain minimum OTC concentration of 5 micrograms/ml of serum were calculated from the t 1/2 and Vd values obtained, using steady-state pharmacokinetics. In the pheasant, the calculated mean IV dose was 23 mg/kg of body weight every 6 hours, whereas the mean IM dose was 43 mg/kg every 24 hours. The mean IM dose was 16 mg/kg every 24 hours for the owl and 58 mg/kg every 24 hours for the parrot. The small volumes required for treatment, the long-dosing interval obtainable, and the broad spectrum of antimicrobial activity of the long-acting OTC preparation studied offered major advantages over other antibiotics commonly used in treating avian species.     

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.