Depletion of intramuscularly and subcutaneously injected procaine penicillin G from tissues and plasma of yearling beef steers.

Withdrawal periods required when doses of 24,000 IU and 66,000 IU of procaine penicillin G/kg body weight were administered to yearling beef steers by intramuscular injection daily for five consecutive days were investigated. These dosages are in excess of product label recommendations, but are in the range of procaine penicillin G dosages that have been administered for the treatment of some feedlot bacterial diseases. The approved dose in Canada is 7,500 IU/kg body weight intramuscularly, once daily, with a withdrawal period of five days. Based on the tissue residue data from this study, the appropriate withdrawal period is ten days for the 24,000 IU/kg body weight dose and 21 days for the 66,000 IU/kg body weight dose when administered intramuscularly to yearling beef steers. In a related study, 18 yearling beef steers received 66,000 IU of procaine penicillin G/kg body weight administered by subcutaneous injection, an extra-label treatment in terms of both dose and route of administration, typical of current practice in some circumstances. Deposits of the drug were visible at subcutaneous injection sites up to ten days after injection, with more inflammation and hemorrhage observed than for intramuscular injections of the same dose. These results suggest that procaine penicillin G should not be administered subcutaneously at high doses; and therefore a withdrawal period was not established for subcutaneous injection.     

Evaluation of route and frequency of administration of three antimicrobial drugs in cattle

This study in six cows compared serum concentrations of trimethoprim and sulphadoxine (16 mg/kg body weight (BW)) after once daily and twice daily administration, and of procaine penicillin G (20,000 IU/kg BW) after subcutaneous (SQ) and intramuscular (IM) administration, and evaluated postmortem tissue concentrations of penicillin following SQ treatment. Trimethoprim and penicillin were measured microbiologically, and sulphadoxine colorimetrically. Using minimum inhibitory concentrations (MIC), trimethoprim reached serum concentrations above 0.5 μg/mL from 15 minutes to 120 minutes, and sulphadoxine exceeded 9.5 μg/mL from 10 minutes to 12 hours, after administration. At 24 hours after treatment, both had declined to below the MIC of most organisms. A second treatment at 12 hours maintained concentrations of sulphadoxine above 9.5 μg/mL for a further 24 hours. For penicillin administered IM and SQ, concentrations that peaked at 0.88 μg/mL would inhibit most common grampositive bacteria for the entire 24 hour period and fastidious gram-negative organisms from 90 minutes to 12 hours after SQ treatment, but for virtually the entire period after IM administration. Mean ± SD concentrations (μg/mL) of penicillin at euthanasia, five days after the last SQ administration, were 1.15 ± 1.27 (injection site), 1.00 ± 0.80 (liver), 0.90 ± 0.58 (renal cortex), 0,58 ± 0.17 (renal medulla), 0.13 ± 0.11 (diaphragm), 0.10 ± 0.08 (gluteal muscle), and 0.06 ± 0.04 (fat). Therefore, except for the most sensitive organisms, twice daily injection of trimethoprim/sulphadoxine (16 mg/kg BW) may be required. Penicillin G administered SQ at 20,000 IU/kg BW should provide effective serum levels for as long as IM administration against gram-positive organisms, but for only about half as long against gram-negative bacteria. The label withdrawal time of five days cannot be used when penicillin is given SQ at 20,000 IU/kg BW for three days.     

Evaluation of plasma concentration after intravenous and intramuscular penicillin administration over 24 hr in healthy adult horses

Penicillin is administered intravenously (IV) or intramuscularly (IM) to horses for the prevention and treatment of infections, and both routes have disadvantages. To minimize these shortcomings, a 24‐hr hybrid administration protocol (HPP) was developed. Our objective was to determine penicillin plasma concentrations in horses administered via HPP. Venous blood was collected from seven healthy horses administered IV potassium penicillin G at 0 and 6 hr and IM procaine penicillin G at 12 hr. Blood was collected at 2‐hr intervals from 0 to 20 hr and at 24 hr. Plasma penicillin concentrations were measured using liquid chromatography and mass spectrometry. Penicillin susceptibility from equine isolates was examined to determine pharmacodynamic targets. The MIC₉₀ of penicillin for 264 isolates of Streptococcus sp. was ≤0.06 μg/ml. For the 24‐hr dosing interval, the mean plasma penicillin concentration was >0.07 μg/ml. Five horses (72%) exceeded 0.06 μg/ml for 98% of the dosing interval, and two horses exceeded this value for 52%–65% of the dosing interval. The HPP achieved mean plasma penicillin concentrations in healthy adult horses above 0.07 μg/ml for a 24‐hr dosing interval. However, individual variations in plasma concentrations were apparent and deserve future clinical study.     

Bovine kidney tissue/biological fluid correlation for penicillin

Penicillin is one of the most commonly misused drugs in steers and dairy cows. In the US, at slaughter the tolerance is 50 ng/g in kidney and other edible tissues. If the tolerance is exceeded, the carcass may not be used for human food. A preslaughter test for penicillin in an easily accessible biological fluid is needed to predict if the concentration of penicillin is below tolerance in the kidney before the bovine is slaughtered. In this study, 12 steers were injected three times with the approved dose (7000 IU) of penicillin at 12-h intervals. Blood and urine samples were collected at intervals after the final dose of penicillin. At each sampling point, one kidney biopsy sample was collected by laparoscopic surgery in the live animal. Another kidney sample was collected at slaughter. Correlations between plasma and kidney concentrations and between urine and kidney concentrations were determined. These correlations predict with 95% confidence that 99% of the animals will have kidney tissue below penicillin tolerance when the plasma concentration of penicillin is below 0.4 ng/mL and/or the urine penicillin concentration is below 140 ng/mL.     

Bioavailability of oral penicillins in the horse: a comparison of pivampicillin and amoxicillin

The pharmacokinetics of ampicillin and amoxicillin following intravenous administration at a dose rate of 15 and 10 mg/kg respectively were studied in four healthy adult horses. Pharmacokinetics of pivampicillin and amoxicillin were studied after oral administration to four healthy adult horses. Pivampicillin, a prodrug of ampicillin, was administered orally to starved and fed horses at a dose rate of 19.9 mg/kg, which is equivalent on a molecular basis to 15 mg/kg ampicillin. Amoxicillin was administered orally to starved horses only, at a dose rate of 20 mg/kg. Ampicillin and amoxicillin concentrations in plasma, synovial fluid and urine were determined. Mean biological half-life of intravenously administered ampicillin and amoxicillin was 1.72 and 1.43 h respectively, whilst the distribution volume (Vss) appeared to be 0.180 and 0.192 1/kg. Orally administered pivampicillin and amoxicillin were rapidly absorbed. A maximum concentration in plasma of 3.80 micrograms/ml was reached 2 h after administration of pivampicillin to starved horses; in fed horses a maximum concentration of 5.12 micrograms/ml was reached 1 h after administration. After oral administration of amoxicillin a maximum concentration of 2.03 micrograms/ml was reached after 1 h. The (absolute) bioavailability of pivampicillin administered orally was 30.9% in starved horses and 35.9% in fed horses. The bioavailability of amoxicillin administered orally was 5.3% in starved horses.     

Penicillin G or ampicillin for oral treatment of canine urinary tract infections.

Penicillin G or ampicillin was administered orally to 144 dogs with urinary tract infections. The daily dosage of penicillin G ranged from 110,000 to 165,000 U/kg (50,000-75,000 U/lb), and the dosage of ampicillin varied from 77 to 110 mg/kg (35-50 mg/lb). The daily dose of each antibiotic was divided into 3 or 4 doses and given at approximately 8- or 6-hour intervals for 10 to 14 days. Response to treatment, based on results of urine culture, varied from no response for infections caused by Pseudomonas spp to 100% response for those caused by Staphylococcus aureus and Streptococcus spp. About 50% of infections caused by Escherichia coli were eliminated, as were about 80% of those due to Proteus mirabilis. Mean concentrations of penicillin G and ampicillin in urines collected at 6-hour intervals after oral administration to clinically normal adult dogs were approximately 350 microgram/ml for both drugs when each was given individually in daily dosages (divided QID) of 55 mg/kg (25 mg/lb). The minimum inhibitory concentration of penicillin G for a number of the bacteria isolated from the urine of the infected dogs was compared with the results of the clinical trials and to the minimum inhibitory concentration of a larger number of urinary bacterial isolates.     

Bioavailability and disposition of sodium and procaine penicillin G (benzylpenicillin) administered orally with milk to calves

Eighteen 1-week-old Holstein calves were randomly assigned to one of three groups: (a) sodium penicillin G administered intravenously, (b) sodium penicillin G administered orally, or (c) procaine penicillin G administered orally. All calves were dosed with penicillin G at 4.0 mg/kg BW. At 5 weeks of age, the calves were dosed again. Blood samples were taken serially for 24 h after both dosings. Plasma was assayed for penicillin G by high performance liquid chromatography (HPLC). For i.v. administration, the area under the concentration-time curve (AUC), 7456 and 5508 ng/mL h, and systemic clearance, 0.54 and 0.73 L/kg h, were significantly different (P < 0.05) at 1 and 5 weeks of age, respectively. There were no significant differences between orally administered sodium and procaine penicillin G within the same age groups. Following oral (p.o.) administration, there were significant differences (P < 0.01) at 1 and 5 weeks of age in the AUC, 760 and 409 ng/mL h, terminal half-life, 2.1 and 1.6 h, time of maximum concentration (TMAX), 3.0 and 2.3 h, and maximum plasma concentration (CMAX), 85 and 58 ng/mL, respectively. Bioavailability was 10.2 and 7.4% at 1 and 5 weeks, respectively.     

Distribution of penicillins into subcutaneous tissue chambers in ponies

The distribution of penicillins into a tissue chamber implanted subcutaneously in ponies was studied. Ampicillin sodium (equivalent to 15 mg/kg ampicillin) was administered intravenously. Pivampicillin, a prodrug of ampicillin, was administered by nasogastric tube to fed ponies at a dose of 19.9 mg/kg (equivalent to 15 mg/kg ampicillin). Procaine penicillin G was administered intramuscularly at a dose of 12 mg/kg (equivalent to 12 000 IU/kg). Six ponies were used for each medication. Antibiotic concentrations in plasma and tissue chamber fluid (TCF) were measured for 24 h after administration. Mean peak concentrations of ampicillin in TCF were 7.3 μg/mL, reached at 1.7 h, and 1.3 μg/mL, reached at 2.7 h, after administration of ampicillin sodium and pivampicillin respectively. The mean peak concentration of penicillin G of 0.3 μg/mL was reached 12.3 h after administration of procaine penicillin G. Concentrations in TCF remained above the minimum inhibitory concentration of Streptococcus zooepidemicus for the proposed dosing intervals of 8, 12 and 24 h for ampicillin sodium, pivampicillin and procaine penicillin G respectively.     

Pharmacokinetics of phenoxymethyl penicillin (penicillin V) in calves

Phenoxymethyl penicillin (penicillin V) was administered intravenously (i.v.) and orally to pre-ruminant calves and the distribution and elimination kinetics, as well as the oral bioavailability, were determined. After i.v. injection, the drug was distributed rapidly in the body, the elimination half-life (t1/2 beta) was 34 min and the apparent volume of distribution at steady-state (Vd ss) was 0.30 l/kg. Mean peak serum drug concentrations were directly related to the oral dose administered, i.e. 0.22 microgram/ml, 1.06 micrograms/ml and 2.14 micrograms/ml after dosing at 10, 20 and 40 mg/kg, respectively. The elimination t1/2 of the drug after oral dosing varied between 90 and 110 min, and the oral bioavailability was approximately 30% of the dose. The co-administration of phenoxymethyl penicillin and probenecid resulted in elevation and prolongation of serum drug concentration. The percentage of drug bound to serum proteins was 78.8% +/- 8.2%. Phenoxymethyl penicillin was probably inactivated and degraded in the gastrointestinal tract of 6-week-old calves fed exclusively hay, silage and concentrates as very low and erratic serum drug concentrations were measured after these calves were dosed orally with the drug at 40 mg/kg. In view of the narrow antibacterial spectrum of the drug and the relatively high dose required, it appears that phenoxymethyl penicillin can only be of limited practical value for the treatment of bacterial infections in preruminant calves.     

Optimal milk penicillin levels for the treatment of experimentally induced mastitis in cows.

Infection of the mammary gland (mastitis) was produced by infusing ten quarters 2/cow x 5 cows) with Staphylococcus aureus strain 305. Mastitic and normal quarters were then infused with a preparation containing two levels of penicillin G (100,000 and 200,000 IU) in 10 mL of 3% aluminum monostearate and peanut oil. Milk penicillin levels were determined prior to treatment and twice daily for eight milkings after treatment. Normal and mastitic quarters infused with 200,000 IU had higher peak levels than those infused with 100,000 IU. Milk penicillin levels were similar in mastitic and normal quarters for the first three milkings after treatment. However, residues persisted for a longer time in milk from mastitic quarters. Penicillin was not detected in milk from the untreated control quarters nor in serum samples assayed during the experiment. The in vitro penicillin G sensitivity of the udder pathogen (MIC=0.039 and MBC=0.078 IU) was well below the milk penicillin levels for the first five milkings in all cases. However, infection recurred in two of the ten quarters (one receiving 100,000 IU and one receiving 200,000 IU).     

Population distributions of phenylbutazone and oxyphenbutazone after oral and i.v. dosing in horses

Experiments to determine the residual plasma concentrations of phenylbutazone and its metabolites found in horses racing on a 'no-race day medication' or 24-h rule were carried out. One dosing schedule (oral-i.v.) consisted of 8.8 mg/kg (4 g/1000 lbs) orally for 3 days, followed by 4.4 mg/kg (2 g/1000 lbs) intravenously on day 4. A second schedule consisted of 4.4 mg/kg i.v. for 4 days. The experiments were carried out in Thoroughbred and Standardbred horses at pasture, half-bred horses at pasture, and in Thoroughbred horses in training. After administering the i.v. schedule for 4 days to Thoroughbred and Standardbred horses at pasture, the mean plasma concentrations of phenylbutazone increased from 0.77 microgram/ml on day 2 to 2.5 micrograms/ml on day 5. The shape of the frequency distribution of these populations was log-normal. These data are consistent with one horse in 1,000 yielding a plasma level of 8.07 micrograms/ml on day 5. After administration of the oral-i.v. schedule to Thoroughbred and Standardbred horses at pasture, the mean plasma concentrations of phenylbutazone were 3.4 micrograms/ml on day 2 and 3.5 micrograms/ml on day 5. The range on day 5 was from 1.4 to 8.98 micrograms/ml and the frequency distribution was log-normal. These data are consistent with one horse in 1000 having a plasma level of 15.8 micrograms/ml on day 5. In a final experiment, the oral dosing schedule was administered to 62 Thoroughbred horses in training. Plasma concentrations on day 5 in these horses averaged 5.3 micrograms/ml. The range was from 1.3 to 13.6 micrograms/ml and the frequency distribution was log-normal. Statistical projection of these values suggests that following this oral dosing schedule in racing horses about one horse in 1000 will yield a plasma level of 23.5 micrograms/ml of phenylbutazone 24 h after the last dose.     

The role of procaine in adverse reactions to procaine penicillin in horses

Procaine penicillin is a commonly used antibiotic in equine medicine but its use is associated with a substantial incidence of adverse reactions. Soluble procaine concentrations were determined by HPLC in several commercially available procaine penicillin preparations, including some that were involved in adverse reactions. The mean (+/- SEM) soluble procaine concentrations in the veterinary preparations was 20.18 +/- 5.07 mg/ml, which was higher than the concentration in the only procaine penicillin preparation for use in humans in Australia of 7.3 mg/ml. Heating the veterinary procaine penicillin preparations to 50 degrees C for 1 day led to a significant (P less than 0.01) increase in the amount of soluble procaine. Heating to 50 degrees C for 7 days also produced a significant (P less than 0.02) increase. Soluble procaine tended to return to baseline concentrations when veterinary procaine penicillin preparations were heated to 50 degrees C for 2 days then stored for 7 days at room temperature. Administration of procaine HCl intravenously (IV) at 2, 5, and 10 mg/kg produced behavioural, locomotor and vascular reactions, which were clinically similar to those reported in adverse reactions to procaine penicillin. The more severe reactions occurred at higher doses, although different horses responded variably at the same dose. Some adverse reactions lead to recumbency but none were fatal. The blood procaine concentrations 1 min after IV administration averaged 19.0 +/- 12.6 and 25.3 +/- 16 micrograms/ml at 2.5 mg/kg and 5 mg/kg, respectively. Ten min after administration, blood procaine concentrations were significantly higher (P less than 0.001) in the 5 mg/kg group than in the 2.5 mg/kg group. Intramuscular (IM) procaine HCl at 5 mg/kg produced significantly lower (P less than 0.001) blood concentrations than similar IV doses, and, in contrast to the IV doses, the amount of procaine in the blood was significantly higher 5 and 10 min after administration than it was after 1 min. Mild excitatory reactions in 4/5 horses were noted 5 to 10 min after IM administration. Administration of diazepam 20 s before procaine HCl prevented the excitatory adverse reaction in 2/2 horses, but administration after the procaine did not influence the outcome.     

Effect of oral administration of dantrolene sodium on serum creatine kinase activity after exercise in horses with recurrent exertional rhabdomyolysis

OBJECTIVE: To determine the effect of oral administration of dantrolene sodium on serum creatine kinase (CK) activity after exercise in horses with recurrent exertional rhabdomyolysis (RER). ANIMALS: 2 healthy horses and 5 Thoroughbreds with RER. PROCEDURE: 3 horses received 2 doses of dantrolene (4, 6, or 8 mg/kg, p.o., with and without withdrawal of food) 2 days apart; 90 minutes after dosing, plasma dantrolene concentration was measured spectrofluorometrically. On the basis of these results, 5 Thoroughbreds with RER from which food was withheld received dantrolene (4 mg/kg) or an inert treatment (water [20 mL]) orally 90 minutes before treadmill exercise (30 minutes, 5 d/wk) during two 3-week periods. Serum CK activity was determined 4 hours after exercise. Plasma dantrolene concentration was measured before and 90 minutes after dosing on the first and last days of dantrolene treatment and before dosing on the first day of the inert treatment period, RESULTS: 90 minutes after dosing, mean +/- SEM plasma dantrolene concentration was 0.62 +/- 0.13 and 0 microg/mL in the dantrolene and inert treatment groups, respectively. Serum CK activity was lower in dantrolene-treated horses (264 +/- 13 U/L), compared with activity in water-treated horses (1,088 +/- 264 U/L). Two horses displayed marked muscle stiffness on the inert treatment. CONCLUSIONS AND CLINICAL RELEVANCE: In 5 horses with RER from which food had been withheld, 4 mg of dantrolene/kg administered orally provided measurable, though variable, plasma concentrations and significantly decreased serum CK activity after exercise in 4 of those horses.     

Antibiotic prophylaxis of lower respiratory tract contamination in horses confined with head elevation for 24 or 48 hours

Objective To evaluate the administration of procaine penicillin prior to or during confinement with head elevation as a means of reducing the associated accumulation of inflammatory lower respiratory tract secretions and increased numbers of bacteria within the lower respiratory tract of confined horses. Design and Procedure Two experiments were conducted to evaluate the efficacy of different dose rates and dosing frequencies. In experiment A a single low dose (15,000 IU/kg) of procaine penicillin was administered to four horses immediately prior to confinement with head elevation for 48 hours. The systemic leucocyte response, gross and cytologic characteristics of transtracheal aspirate and bacterial numbers in lower respiratory tract samples were compared with corresponding samples from two horses confined with heads elevated but not given penicillin. The efficacy of higher dose rates (20,000 IU/kg and 40,000 IU/kg) given before and during confinement with heads elevated for 24 hours was evaluated in experiment B. Results Treatment with procaine penicillin had no effect on the systemic leucocyte response or on the accumulation of inflammatory lower respiratory tract secretions at any of the dosing schedules evaluated. The number of bacteria isolated from trans-tracheal samples was reduced at 12 hours for treated horses in experiment A and at 24 hours for experiment B. β-haemolytic Streptococcus spp were not isolated from treated horses in either experiment. Bacterial species isolated from treated horses were predominantly Pasteurella and/or Actinobacillus spp, however, members of the family Enterobacteriaceaé and a Staphylococcus sp were isolated from treated horses. One treated horse in experiment A developed clinically apparent pulmonary disease. Conclusions The prophylactic administration of penicillin before or during confinement did not reliably reduce bacterial numbers or prevent the accumulation of purulent lower respiratory tract secretions in horses confined with their heads elevated. Numbers of β-haemolytic Streptococcus spp were reduced following treatment, suggesting that the repeated administration of procaine penicillin may have some merit as part of a strategy to prevent transport-associated respiratory disease. However, methods directed at minimising the duration of confinement with head elevation, augmentation of the clearance of accumulated secretions and prompt identification of animals in which airway inflammation has extended to the pulmonary parenchyma remain the best ways of minimising transport-associated respiratory disease.     

Pharmacokinetics of probenecid and the effect of oral probenecid administration on the pharmacokinetics of cefazolin in mares

The pharmacokinetics and bioavailability of probenecid given IV and orally at the dosage level of 10 mg/kg of body weight to mares were investigated. Probenecid given IV was characterized by a rapid disposition phase with a mean half-life of 14.0 minutes and a subsequent slower elimination phase with a mean half-life of 87.8 minutes in 5 of 6 mares. In the remaining mare, a rapid disposition phase was not observed, and the half-life of the elimination phase was slower (172 minutes). The mean residence time of probenecid averaged 116 minutes for all 6 mares and 89.2 minutes for the 5 mares with biphasic disposition. The total plasma clearance of probenecid averaged 1.18 +/- 0.49 ml/min/kg, whereas renal clearance accounted for 42.6 +/- 9.3% of the total clearance. The steady-state volume of distribution of probenecid averaged 116 +/- 28.2 ml/kg. Plasma protein binding of probenecid was extensive, with 99.9% of the drug bound at plasma probenecid concentrations of 10 micrograms/ml. The maximum plasma probenecid concentration after 10 mg/kg orally averaged nearly 30 micrograms/ml. The half-life of probenecid after oral administration was approximately 120 minutes. Oral bioavailability was good with greater than 90% of the dose absorbed. The effect of probenecid on tubular secretion of organic anions was evaluated by determining the pharmacokinetics of IV cefazolin (11 mg/kg) administered alone and 15 minutes after probenecid (10 mg/kg orally). Treatment with probenecid did not affect pharmacokinetic values of cefazolin. This failure of probenecid to alter the pharmacokinetics of cefazolin may be caused by insufficient plasma probenecid concentrations after the oral dose.     

Evaluation of the oral vitamin E absorption test in horses

An oral vitamin E absorption test used in human beings was modified for use in horses. The most appropriate techniques with which to measure gastrointestinal tract absorption of vitamin E (alpha-tocopherol) in horses were developed. Vitamin E was administered orally, and serum values of alpha-tocopherol were measured by use of high-performance liquid chromatography at 0, 3, 6, 9, 12, and 24 hours after vitamin E administration. Variables included comparison of 2 dosages (45 and 90 IU/kg of body weight), routes of administration, and absorption dynamics of 3 preparations of dl-alpha-tocopherol. Absorption of the 2 doses of dl-alpha-tocopherol acetate indicated a dose response; the area under the curve at 24 hours (AUC24) was 4.3 micrograms.h/ml for the 45-IU/kg dose and 32.2 micrograms.h/ml (P less than 0.01) for the 90-IU/kg dose. Maximal absorption was apparent when vitamin E was naturally consumed in grain, compared with administration of identical preparations by stomach tube or paste. In the same horses, dl-alpha-tocopherol and dl-alpha-tocopherol acetate plus polyethylene glycol had statistically similar absorption curves and both had significantly greater AUC24, compared with dl-alpha-tocopherol acetate; values for the 3 compounds were 23.6, 25.8, and 12.6 micrograms.h/ml, respectively. The AUC24 varied between individual horses, but time of peak value was consistently observed between 6 and 9 hours.(ABSTRACT TRUNCATED AT 250 WORDS)     

Kinetics and residues after intraperitoneal procaine penicillin G administration in lactating dairy cows

This paper describes the pharmacokinetic profile of procaine penicillin G after intraperitoneal (IP) administration in eight lactating dairy cows. Procaine pencillin G (PPG, 21 000 IU/kg) was deposited into the abdominal cavity of each cow following an incision in the right paralumbar fossa. Blood and milk samples were taken over the following 10 days, at which point the cows were euthanized. Plasma, milk, muscle, liver, and kidney penicillin concentrations were determined by HPLC, with a limit of quantification of 5 ng/mL for plasma and milk and 40 ng/g for tissue samples. A noncompartmental method was used to analyze plasma kinetics. The mean pharmacokinetic parameters (±SD) were: C _max, 5.5 ± 2.6 μg/mL; T _max, 0.75 ± 0.27 h; AUC _0-∞, 10.8 ± 4.9 μg·h/mL; MRT , 2.2 ± 0.9 h. All milk from treated cows contained detectable penicillin residues for a minimum of three milkings (31 h) and maximum of five milkings (52 h) after administration. Concentrations of penicillin in all muscle, liver, and kidney samples taken 10 days postadministration were below the limit of quantification. Necropsy examinations revealed foci of hemorrhage on the rumenal omentum of most cows but peritonitis was not observed. Systemic inflammation as determined by change in leukogram or plasma fibrinogen was noted in one cow. The results of this study demonstrate that IP PPG is absorbed and eliminated rapidly in lactating dairy cows.     

The Influence of Detomidine and Epinephrine on Heart Rate, Arterial Blood Pressure, and Cardiac Arrhythmia in Horses

Detomidine (10 micrograms/kg and 20 micrograms/kg) was administered to seven horses with and without epinephrine infusion (0.1 microgram/kg/min) from 5 minutes before to 5 minutes after detomidine injection. One or more single supraventricular premature heartbeats were observed in three horses after detomidine administration. Epinephrine infusion did not modify the incidence of cardiac arrhythmias in detomidine-treated horses at the doses tested. Relatively high momentary peak systolic pressures were registered in some horses after detomidine administration during epinephrine infusion. The highest systolic arterial blood pressure was 290 mm Hg, but this value was not higher than that reported in horses during maximum physical exercise. Epinephrine infusion did not alter blood gases, arterial pH, or base excess.     

Clinical efficacy of trimethoprim/sulfadiazine and procaine penicillin G in a Streptococcus equi subsp. zooepidemicus infection model in ponies

Tissue chambers, implanted subcutaneously on both sides of the neck in eight ponies, were inoculated with Streptococcus equi subsp. zooepidemicus in order to compare the clinical efficacy of trimethoprim/sulfadiazine (TMP/SDZ) and penicillin G treatment in a purulent infection. The TMP/SDZ treatment consisted of one intravenous (i.v.) injection of 5 mg/kg TMP and 25 mg/kg SDZ and the same dose of TMP/SDZ per os (p.o.), both given 20 h after inoculation. The oral dose was then repeated every 12 h for 21 days. The penicillin treatment consisted of one i.v. injection of 20 000 IU/kg sodium penicillin G and intramuscular (i.m.) injection of 20 000 IU/kg procaine penicillin G, both given 20 h after infection. The i.m. dose was then repeated every 24 h for 21 days. Eight ponies, each with two tissue chambers, were used in a cross over design; in the first experiment the left tissue chamber (TC) was infected and in the second experiment the right. TMP/SDZ treatment resulted in a limited reduction of viable bacteria in the TC but did not eliminate the infection, resulting in abscessation in 10-42 days in all eight ponies. However, penicillin treatment eliminated the streptococci in seven of eight ponies, and only one pony suffered abscessation on day 10. This constitutes a significantly better efficacy of the penicillin treatment in this model. The most probable cause of the failure of TMP/SDZ to eliminate the streptococci is inhibition of the action of TMP/SDZ in the purulent TCF. Therefore, TMP/SDZ should not be used to treat purulent infections in secluded sites in horses.     

Pharmacokinetics and pharmacodynamics of epsilon-aminocaproic acid in horses

OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of epsilon-aminocaproic acid (EACA), including the effects of EACA on coagulation and fibrinolysis in healthy horses. ANIMALS: 6 adult horses. PROCEDURES: Each horse received 3.5 mg of EACA/kg/min for 20 minutes, i.v. Plasma EACA concentration was measured before (time 0), during, and after infusion. Coagulation variables and plasma alpha(2)-antiplasmin activity were evaluated at time 0 and 4 hours after infusion; viscoelastic properties of clot formation were assessed at time 0 and 0.5, 1, and 4 hours after infusion. Plasma concentration versus time data were evaluated by use of a pharmacokinetic analysis computer program. RESULTS: Drug disposition was best described by a 2-compartment model with a rapid distribution phase, an elimination half-life of 2.3 hours, and mean residence time of 2.5 +/- 0.5 hours. Peak plasma EACA concentration was 462.9 +/- 70.1 microg/mL; after the end of the infusion, EACA concentration remained greater than the proposed therapeutic concentration (130 microg/mL) for 1 hour. Compared with findings at 0 minutes, EACA administration resulted in no significant change in plasma alpha(2)-antiplasmin activity at 1 or 4 hours after infusion. Thirty minutes after infusion, platelet function was significantly different from that at time 0 and 1 and 4 hours after infusion. The continuous rate infusion that would maintain proposed therapeutic plasma concentrations of EACA was predicted (ie, 3.5 mg/kg/min for 15 minutes, then 0.25 mg/kg/min). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that EACA has potential clinical use in horses for which improved clot maintenance is desired.