Acute phase protein concentrations following serial procaine penicillin G injections in horses.

BACKGROUND: Acute phase protein (APP) measurement is used to detect inflammation. Intramuscular (IM) injections could cause tissue injury and induce an acute phase response (APR). OBJECTIVES: To evaluate the effects of IM procaine penicillin G (PPG) injections on APP concentrations in horses. STUDY DESIGN: Prospective longitudinal design. METHODS: PPG was administered intramuscularly to six horses, twice daily, for 5 days. Plasma fibrinogen (FIB), serum amyloid A (SAA), haptoglobin (HAP), creatine kinase (CK), and aspartate aminotransferase (AST) were quantified daily for 5 days before the first injection, during the course of administration, and for 4 days after the final dose. Analytes were quantified every other day for the remaining 16 days. Data were compared using a parametric or non-parametric repeated measures ANOVA and a Tukey's or Mann-Whitney rank sum test, respectively. Significance was set at p < 0.05. RESULTS: CK was increased over baseline (mean ± SD: 200 ± 74 IU/L) on Days 1-6 (p < 0.001 to p = 0.02, mean ± SD: 723-1177 ± 355-544 IU/L) and AST was increased above baseline (mean ± SD: 233 ± 58 IU/L) on Days 2-7 and 10 (p < 0.001 to p = 0.05, mean ± SD: 307-437 ± 79-146 IU/L). Increased FIB was noted over baseline (mean ± SD: 177 ± 30 mg/dl) on Days 6-8 and 10 (p = 0.02 to p = 0.03, mean ± SD: 234-252 ± 33-49 mg/dl). SAA was increased above baseline (mean ± SD: 4.7 ± 2.9) on Day 6 (p = 0.02, mean ± SD: 113 ± 186 µg/ml). There was no change in HAP. MAIN LIMITATIONS: Healthy horses were used, small sample size, and a lack of a negative control group. CONCLUSIONS: Serial intramuscular procaine penicillin G (IM PPG) injections may result in increased positive APP concentrations in horses and this must be considered when these test results are interpreted.

Effect of the injection site on the pharmacokinetics of procaine penicillin G in horses.

The plasma penicillin concentrations were determined in 5 horses given an IV injection of sodium penicillin G; plasma penicillin concentrations were also determined in a crossover experiment, where animals were given procaine penicillin G subcutaneously at 1 site and IM at 4 sites. The mean penicillin plasma peak concentration and bioavailability were highest after the drug was injected in the neck and biceps musculature. Injections in the gluteal muscle and in the subcutaneous sites resulted in similar, but lower, more persistent penicillin plasma concentrations and a lower bioavailability than were obtained with injection in the neck and biceps musculature. The pharmacokinetic data obtained after penicillin was administered via the pectoral muscle route exhibited an intermediate position. Therapeutic implications of the routes of administration with respect to hemolytic streptococcal infections are discussed.

Plasma and tear concentrations of antibiotics administered parenterally to cattle.

Chloramphenicol, erythromycin, gentamicin, oxytetracycline, penethamate and procaine benzyl penicillin were administered parenterally to cattle and the concentrations of these antibiotics in plasma and tears were assayed microbiologically. Concentrations in plasma and tears were significantly correlated for all antibiotics tested but the concentration of antibiotic in tears and the tear flow rate were not correlated. Lipophilic drugs diffused into the tears in higher concentrations than did drugs which were not lipophilic. Concentrations of lipophilic but not hydrophilic antibiotics in tears could be predicted from the Henderson-Hasselbach equation. In cattle, it is possible through parenteral administration of chloramphenicol, erythromycin, gentamicin or oxytetracycline to achieve antibiotic concentrations in the tears which are bacteriostatic to Moraxella bovis, a primary aetiological agent of infectious bovine keratoconjunctivitis.

Serum concentration of penicillin in the horse after repeated intramuscular injections of procaine penicillin G alone or in combination with benzathine penicillin and/or phenylbutazone.

Twenty-one adult horses were randomly assigned into 7 groups of 3 and were treated for 5 days with procaine penicillin G, benzathine penicillin , or phenylbutazone in various combinations and dosage schedules. Serum concentration of penicillin was measured serially over a 7-day period. The highest mean peak serum concentration was 2.06 micrograms/ml. Comparable peak values were seen 2 to 4 hours after administration of 22,000 IU of procaine penicillin G/kg of body weight given once or twice daily. A minimum serum concentration of 0.25 micrograms/ml was selected as adequate for efficacy against organisms that can be considered sensitive to penicillin. Once daily administration of procaine penicillin G and, although peak concentrations were lower, some regimens of procaine and benzathine penicillin G did maintain this concentration. Concurrent phenylbutazone administration did not affect serum concentration of penicillin appreciably.

Procaine in the urine of racing Greyhounds: possible sources.

Greyhounds (n = 25) were given procaine in the form of procaine HCl or procaine penicillin G or were fed meat prepared from a heifer given procaine penicillin G on 3 consecutive days before slaughter. Dogs given procaine HCl or procaine penicillin G were given daily doses equivalent to 9 mg of procaine/kg. Urine samples were collected from the dogs twice daily before dosing, during the dosing period, and for 4 days after final dose administration. All dogs excreted detectable concentrations of procaine in the urine, regardless of the dose form or route of administration. Blood plasma samples were prepared from 10 Greyhounds to determine procaine esterase activity. Hydrolysis of procaine by plasma esterases did not occur. Low plasma procaine esterase activity, coupled with rapid oral absorption of procaine, resulted in high urinary concentrations of the parent drug in dogs given procaine HCl or procaine penicillin G (9 mg/kg). Even in the dogs given relatively small doses (0.85 mg/kg) of procaine in the form of meat residues, urinary procaine concentrations were found. The results of these studies indicate that procaine is rapidly absorbed following oral administration and that meat from livestock given procaine penicillin before slaughter may serve as a source of urinary procaine in Greyhounds consuming the meat.

Excretion rates of antibiotics in milk of sheep and their effect on yogurt production.

Excretion rates in milk of sodium penicillin G, streptopenicillin, oxytetracycline, and chlortetracycline given to sheep by intramuscular injection or intramammary infusion were studied. When given by intramuscular injection, penicillin G and streptopenicillin were excreted in milk for 24 h, oxytetracycline for 38 h, and chlortetracycline for 72 h. The corresponding times following intramammary infusion were 72 to 86 h, 72 to 86 h, 96 to 100 h, and 110 to 120 h. Concentrations in milk of penicillin, streptopenicillin, and oxytetracycline given by intramuscular injection made it unsuitable for yogurt production for 24 h. Chlortetracycline, although excreted in milk longer, did not affect yogurt production. When antibiotics were given by intramammary infusion, they were excreted in milk in concentrations harmful for yogurt production for 72, 72, 96, and 116 h.

[An experimental study on pyogenic osteomyelitis with special reference to the analysis of the therapeutic effects of antibiotics in vivo (author's transl)].

Experimental osteomyelitis was produced in mice by the Ueno's method for the purpose of evaluating therapeutic effects of the antibiotics. The results were as follows: 1) Experimental osteomyelitis produced with penicillin-G sensitive bacteria was completely cured by PC-G 1.8 mg per mouse a day, which provided maintenance of the concentration in serum more than 10 times of MIC for over 12 hours. The dosis of 0.18 mg per mouse per day was insufficient to bring a complete healing. 2) Experimental osteomyelitis produced with penicillin-G resistant bacteria did not heal completely, despite the administration of MPI-PC, a synthetic penicillin designed against penicillin resistant staphylococci, in a dosis of 5 mg twice a day, probably by the following reasons. Since MPI-PC is water-soluble, it is difficult to maintain the concentration in serum more than 10 times of MIC for over 1 hour. In other word, the bacteria was exposed to the effective antibiotic concentration for only one hour twice a day. 3) It was experimentally proved that earlier administration of antibiotics following inoculation provided quicker elimination of bacteria. 4) When bactericidal antibiotics were used, administration twice a day in half dosis gave better results compared with the full dosis once a day. 5) This experimental model of osteomyelitis proved quite useful for quantitative analysis of the effects of antibiotics, which would be applicable as a good method for evaluation of antibiotics to be developed in the future.

Systemic toxic reactions to procaine penicillin G.

Systemic toxic were encountered in eight of 10,469 patients during or immediately following the intramuscular injection of 4,800,000 units of procaine penicillin G for the treatment of gonorrhea. Fear of imminent death, visual and auditory disturbances, violent combativeness, confusion, disorientation, and restlessness, disturbance in taste, cardiovascular changes, and grand mal seizures are the principal manifestations; these usually subside in two to 10 minutes spontaneously or after treatment. Symptoms and signs closely parallel systemic toxic reactions to local anesthetics. Pharmacokinetic analysis in dogs using 14C-procaine and 14C-procaine penicillin G showed rapid distribution of labeled drugs from plasma to cerebrospinal fluid for the intravenous as compared to the intramuscular route of administration. The animal studies were consistent with the hypothesis that the inadvertent intravenous administration of procaine penicillin G is responsible for the systemic toxic reactions. Plasma procainesterase (pseudocholinesterase) activity was assayed with an ultraviolet spectroscopic method. Substrates were procaine and procaine penicillin G. The plasma procainesterase activity of patients who had experienced systemic toxic reactions was significantly decreased as compared to that of controls, an observation not previously reported.

Variable rachitogenic effects of grain and alleviation by extraction or supplementation with vitamin D, fat and antibiotics.

Three experiments were conducted using day-old broiler type chicks to determine the effect of different cereal grains on vitamin D3 utilization and to investigate the effects of rye, corn, wheat and triticale as the cereal grain component of the diets on the development of a rachitic condition in chicks. Rye was submitted to acid treatment and water extraction in an attempt to destroy or isolate the rachitogenic factor. Results showed that with chicks fed a diet containing 200 I.U. of vitamin D3 with corn as the grain, mineralization of their bones was normal. Growth and bone ash were depressed when rye replaced corn in the diet. These effects were partially reversed when either fat or procaine penicillin was added to the diet, and comppletely prevented with a high level of vitamin D3 (2,000 I.U./kg.). In another experiment, triticale depressed bone ash even though it did not affect body growth to the same extent as rye. Our results indicate that the factor responsible for the rachitogenic condition of rye-fed chicks can be removed by water extraction of this grain or partially destroyed by acid autoclaved treatment. A combination of acid autoclaved treatment and penicillin supplementation prevented the depression in bone ash.

Nonlactating-cow therapy with a formulation of penicillin and novobiocin: mammary irritation and residues.

An experimental product incorporating 500,000 IU of procaine penicillin G and 600 mg of sodium novobiocin in 2% aluminum monostearate-peanut oil gel (10-ml dose) was infused after the final milk-out at end of lactation into all 4 mammary quarters of 56 cows that were infected in at least 1 quarter. The therapeutic and prophylactic efficacies were published in the companion report. Infusion of the product in all quarters of 5 lactating cows resulted in only slight irritation. Penicillin was eliminated by the 11th milking and novobiocin by the 5th. After infusion in the dry udder, the antibiotics were no longer detectable in serous secretion after 14 days and failed to appear in urine at the earliest (7-day) sampling after administration. Neither antibiotic was detectable in the 1st postpartum milking after nonlactating periods as short as 3 weeks.

Comparison of two methods for detecting antibiotic residues in slaughter animals.

A comparison was made of the sensitivity of two methods in current use for the detection of antibiotic residues in slaughter animals. Calves previously given therapeutic injections of an antibiotic were used and a variety of samples were tested.