Effect of transportation on lower respiratory tract contamination and peripheral blood neutrophil function

Objective To evaluate the effect of transportation on lower respiratory tract contamination and peripheral blood neutrophil function in horses and to compare results from transported horses with those obtained in earlier experiments from horses confined with heads elevated. Design A prospective study. Procedure Six horses were transported by road for 12 h. Clinical and haematological examination, transtracheal aspiration and cell function studies were conducted before and after transportation. Results obtained after transportation were compared to pre-transportation values. Results After transportation, peripheral blood leucocyte and neutrophil numbers were increased and rectal temperatures were elevated. Transtracheal aspirates showed an accumulation of purulent respiratory tract secretions with increased numbers of bacteria, particularly β-haemolytic Streptococcus spp and members of the Pasteurellaceae family. Three horses also had increased numbers of bacteria from the Enterobacteriaceae family relative to corresponding samples from earlier studies. Phagocytosis by peripheral blood neutrophils was significantly reduced, while the oxidative burst activity of peripheral blood leucocytes was either unchanged or enhanced. Clinical Implications Bacterial contamination of the lower respiratory tract occurs as a routine consequence of transportation of horses and is likely to be an important determinant in the development of transport-associated respiratory disease. Inflammatory airway secretions and increased numbers of bacteria were rapidly cleared, without clinical evidence of significant pulmonary disease and without additional treatment, in normal horses that were allowed to lower their heads after transportation. Peripheral blood neutrophilia and a reduction in neutrophil phagocytic function were evident for at least 36 h after transportation, suggesting that horses may require a number of days to recover from the stress of transportation. As the potential role of bacteria from the Enterobacteriaceae family in the development of transport-associated respiratory disease has not been elucidated, horses which develop clinical disease following transportation should undergo thorough bacteriological investigation to ensure appropriate treatment.     

Inflammation and increased numbers of bacteria in the lower respiratory tract of horses within 6 to 12 hours of confinement with the head elevated

SUMMARY: Confinement of horses with their heads elevated for periods up to 24 hours was used to evaluate the extent and the effects of bacterial contamination of the equine lower respiratory tract. Significant (P < 0.05) increases in bacterial numbers (up to 10⁹ colony forming units/mL in transtracheal aspirate derived samples) occurred within 6 or 12 hours in most horses. Pasteurella/Actinobacillus spp and Streptococcus spp were most commonly isolated. Lowering of the head for 30 minutes every 6 hours to facilitate postural drainage did not prevent multiplication of organisms to levels equivalent to those achieved by horses where the head was elevated for 24 hours. When horses were released from confinement and heads were no longer maintained in an elevated position, clearance of accumulated secretions and bacteria occurred within 8 to 12 hours. Thus, confinement with the head elevated resulted in significant bacterial contamination and multiplication within the lower respiratory tract during a period often encountered in routine management procedures, such as transportation. The clearance of accumulated secretions occurred over a prolonged period after release from such confinement.     

Effects of posture and accumulated airway secretions on tracheal mucociliary transport in the horse

Tracheal mucociliary clearance was determined in horses by measuring the rostrad transport of the radiopharmaceutical ^99mtechnetium-sulphur colloid following deposition on the tracheal epithelium by intratracheal injection. The effects of head position (head elevated to normal standing position vs head lowered) and of accumulated purulent secretions on tracheal mucociliary clearance were evaluated for the first time in the horse. In normal horses tracheal mucociliary clearance was greatly accelerated by lowering the head so that the cranial trachea was lower than the caudal trachea. Horses confined with their heads elevated for 24 hours developed an accumulation of purulent airway secretions (and associated increased numbers of bacteria) in the lower respiratory tract and showed a decrease in tracheal mucociliary clearance when compared with their previously measured rate when the lower airway contained only normal secretions. These findings have implications for management practices where horses are prevented from lowering their heads, such as transportation and cross-tying, which may therefore contribute to lower respiratory tract disease in horses.     

Influence of head posture on the respiratory tract of healthy horses

Twenty four normal, confined mares were unable to lower their heads for 24 or 48 h. In 21 mares this resulted in increases in the proportion of neutrophils and/or numbers of bacteria in transtracheal aspirates. In eight mares the changes in tracheal washes were accompanied by clinical evidence of mild respiratory disease. In three additional cases respiratory signs were accompanied by systemic illness. These changes reversed once the mares were able to lower their heads. Haematological changes (absolute neutrophilia and/or hyperfibrinogenamia) were mild and occurred more commonly in horses restrained for 48 h. The results suggest that keeping the heads of healthy horses raised leads to an increased bacterial burden in their tracheobronchial secretions. These changes appeared to be related to head posture effects and not simply confinement in stocks. These findings give further weight to the theory that postural drainage may facilitate clearance of bacteria from the tracheobronchial tree. The possible relevance of such findings to post-transportation pneumonia in horses is discussed.     

Anaerobic bacterial pneumonia with septicemia in two racehorses

Anaerobic bacterial pneumonia with septicemia was diagnosed in 2 Thoroughbred racehorses referred with respiratory tract disease that had failed to respond to initial treatment with various antibiotics including penicillin and trimethoprim-sulfamethoxazole. Multiple anaerobic organisms, including Bacteroides spp and Fusobacterium spp, were isolated from blood and transtracheal aspirates obtained from both horses and from aspirates of cutaneous nodules obtained from 1 horse. The latter horse responded to metronidazole treatment followed by procaine penicillin G administration and regained its health over the following 6 months. The other horse did not respond as favorably to a similar antibiotic regimen and died following an acute episode of pulmonary hemorrhage after remaining intermittently febrile for 7 weeks. Although in vitro antimicrobial susceptibility tests indicated that all anaerobic organisms isolated from both horses were susceptible to penicillin, the infection in these horses responded poorly to initial treatments with this drug. We speculated that adequate penicillin concentration was not attained in the deep foci of infection in the lungs. Animals with anaerobic bacterial infections that fail to respond to penicillin or from which penicillin-resistant anaerobes are isolated may benefit from treatment with metronidazole.     

Retropharyngeal lymph node infection in horses: 46 cases (1977–1992)

SUMMARY A retrospective study of 46 horses with retropharyngeal lymph node (RPLN) infection presented to the Rural Veterinary Centre between 1977 and 1992 was undertaken. Horses aged less than one year were most commonly represented (46%). Thirty-nine percent of cases had been exposed to horses with confirmed or suspected strangles (Streptococcus equi subsp equi infection) within the previous 8 weeks. Most frequent signs were unilateral or bilateral swelling of the throat region (65%), respiratory stertor/dyspnoea (35%), purulent nasal discharge (20%), inappetence and signs of depression (15%), and dysphagia (9%). All horses had a soft tissue density in the retropharyngeal region on radiographs. Rhinopharyngoscopy, ultrasonography, haematology as well as cytological and microbial analysis of material aspirated from the soft tissue swelling facilitated diagnosis in some horses. Fifteen horses (33%) were treated with procaine penicillin intramuscularly for 4 to 7 days followed by oral trimethoprim-sulphadimidine for 7 to 14 days. Non-steroidal anti-inflammatory drugs were administered to 6 horses. Four required tracheostomy for severe respiratory distress. The 15 horses treated medically responded to treatment and were discharged from hospital. Three horses (6%) with mild signs received no treatment and recovered uneventfully. Twenty-eight horses (61%) underwent general anaesthesia and surgical drainage of a RPLN abscess. Nineteen received procaine penicillin G for 4 to 7 days. Four of the nine horses that did not receive antibiotic treatment after surgery required further surgical drainage 10 days to 7 weeks after the initial surgery . Limited follow-up information was available for 37 horses. Thirty-two horses were considered to have made complete recovery, 3 horses had died through misadventure and 2 had been euthanased because of chronic ill-thrift .     

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.     

Canine pedal dermatitis due to percutaneous Uncinaria stenocephala infection

Related to its potential vulnerability the respiratory tract has a very complex and effective defence apparatus. The interaction between these defence mechanisms and certain characteristics of aetiological agents results in a pattern in which initial infections by these agents tend to occur at specific sites in the tract.

Infections in which the primary portal of entry is in the upper respiratory tract include Bordetella bronchiseptica and Haemophilus spp in pigs; Pasteurella spp in cattle, sheep, pigs; Mycoplasma spp in cattle, sheep, pigs and poultry; equine herpesvirus 1 in horses; infectious bovine rhinotracheitis in cattle; parainfluenza 3 in cattle and sheep; infectious laryngo-tracheitis and infectious bronchitis in poultry; feline viral rhinotracheitis and calicivirus in cats; Aujeszky' disease virus and swine influenza in pigs; and equine influenza in horses. Infections in which the primary portal of entry is in the lower respiratory tract include Aspergillrrs fumigatus in poultry and mammals, respiratory syncytial virus in cattle, distemper virus in dogs and adenovirus in cattle and dogs. A fuller understanding of the interactions between an agent and the host at the point of entry would make it much easier to develop effective vaccines and therapeutic agents.     

Administration of Perioperative Penicillin Reduces Postoperative Serum Amyloid A Response in Horses Being Castrated Standing

Objectives: To compare postoperative inflammatory responses in horses administered perioperative procaine penicillin and those not administered penicillin using acute phase protein serum amyloid A (SAA) as a marker of inflammation. Study Design: Randomized clinical trial. Animals: Stallions (n=50) castrated under field conditions. Methods: SAA concentrations were determined on days 0, 3, and 8. Six horses were subsequently excluded because of elevated SAA concentrations on day 0. Of the remaining 50 horses, 26 were administered nonsteroidal anti‐inflammatory drug (NSAID) therapy and 24 were administered NSAID and 25,000 U/kg procaine penicillin on day 0, 1, and 2. Results: SAA concentrations increased significantly from preoperative levels in both groups, and on day 8 concentrations were significantly (P<.02) higher in horses administered only NSAID than in those administered procaine penicillin and NSAID. Infectious complications occurred more frequently (P<.01) in horses with preoperatively elevated SAA concentrations (the excluded horses) than in horses with normal preoperative SAA concentrations (the included horses). Conclusions: Perioperative antimicrobial therapy reduced the postoperative SAA response, suggesting that bacteria were present in the surgical wound and contributed to inflammation after castration. Horses with elevated preoperative SAA concentrations developed infectious complications more often than horses with normal preoperative SAA concentrations. Clinical Relevance: Administration of antimicrobials may be important in horses being castrated standing under field conditions. Increased SAA concentrations seem to be an indicator of increased surgical risk in horses and may be useful before elective surgery for planning.     

An investigation of the incidence of chronic obstructive pulmonary disease (COPD) in random populations of Swiss horses

The incidence of Chronic Obstructive Pulmonary Disease (COPD) in Switzerland was determined in three groups of horses selected at random. Group A (97 horses) and Group B (93 horses) had no history of respiratory disease, but Group C (113 horses) had a history of lower respiratory tract disease. All horses were examined by auscultation of the respiratory tract under forced breathing, endoscopic examination of the upper and lower respiratory tract, arterial blood gas analysis at rest and cytological examination of respiratory secretions (RS). Fifty-four per cent of the horses in Group A and 54.8 per cent of Group B were diagnosed as suffering clinical COPD and only 12.4 per cent of horses in Group A and 8.6 per cent in Group B had no detectable abnormalities in their lower respiratory tracts. In Group B, 19.4 per cent were considered to be suffering from parasitic pulmonary disease indicated by elevated numbers of eosinophils in their RS. Pharyngeal lymphoid hyperplasia was exhibited in 70.1 per cent of Group A and 74.2 per cent of Group B. Cytological examination of RS was useful to determine if the secretions found in the trachea originated from the upper or lower respiratory tract. Arterial blood gas analysis revealed no significant differences between healthy horses and those with subclinical or mild COPD.     

Benzathine Penicillin G and Procaine Penicillin G in Piglets: Comparison of Intramuscular and Subcutaneous Injection

The disposition of penicillin G in piglets is described after intramuscular or subcutaneous injection of depot preparations. The piglets were injected with 33 000 IU/kg or 100 000 IU/kg benzathine + procaine penicillin G intramuscularly or subcutaneously, or 100 000 IU/kg procaine penicillin G intramuscularly or subcutaneously. Intramuscular injection of benzathine + procaine penicillin resulted in higher maximum concentration in plasma (C_max) than did subcutaneous injection. The mean residence time (MRT) of penicillin G was longer when the drugs were injected subcutaneously rather than intramuscularly. The plasma concentration versus time profiles of the subcutaneous injections of benzathine + procaine penicillin revealed secondary peaks, possibly reflecting a certain degree of inflammation at the injection site.     

Clinical signs and etiology of adverse reactions to procaine benzylpenicillin and sodium/potassium benzylpenicillin in horses

Case reports of 59 horses reacting adversely to procaine benzylpenicillin or to sodium or potassium benzylpenicillin in Sweden in 2003-2005 were obtained through contacts with horse-owners. For the assessment of the reports, various parameters were evaluated, such as the times to the reactions, information on previous penicillin treatment, the clinical signs and the actions taken in the reacting horses. Among the reports, two horses had received sodium or potassium benzylpenicillin intravenously, whereas the remaining 57 horses had been treated with procaine benzylpenicillin intramuscularly. Allergy may underlie the adverse reactions in the horses given sodium and potassium benzylpenicillin, and in a few of the horses given procaine benzylpenicillin. However, in most horses in the latter group, the clinical signs may be due to the toxic effects of procaine. In these horses, the dominating clinical signs were locomotor and behavioral changes. Some risk factors may enhance the probability that horses react to procaine. One is repeated injections, which increase the likelihood of intravascular administration and also may increase the sensitivity to procaine due to neuronal sensitization (kindling). Procaine is rapidly hydrolyzed by plasma esterases to nontoxic metabolites. When high amounts of procaine enter the circulation, the hydrolyzing capacity may be exceeded and toxicity occurs. Analyses of plasma esterases from reacting horses showed lower activity than in nonreacting control horses. Low esterase activity may increase the possibility of procaine toxicity and constitute another risk factor.     

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.     

Blood culture status in mature horses with diarrhoea: A possible association with survival

Reasons for performing study: The incidence and implications of positive blood cultures in mature horses with diarrhoea is unknown. The diagnosis of bacteraemia may alter treatment and prognosis. Hypothesis: The proportion of horses with diarrhoea that are blood culture positive is higher than previously assumed and a positive blood culture has a negative impact on survival. Methods: Blood cultures were taken at admission and 24 h after admission from 31 mature horses with diarrhoea. Results: Nine (29%) horses were blood culture positive within 24 h of admission. Organisms isolated included Corynebacterium spp. (n = 6), Streptococcus spp. (n = 2), Pantoea agglomerans (n = 1), Gram‐negative rod (n = 1), Bacillus spp. (n = 1) and yeast (n = 1). Horses with positive blood cultures were significantly less likely to survive. Prior treatment with antimicrobial drugs had no significant effect on blood culture status. Horses with positive blood cultures had a significantly higher heart rate, packed cell volume (PCV) and plasma potassium concentration at admission, and a higher PCV and lower total plasma protein concentration 24 h after admission. Conclusions: Positive blood cultures occur more frequently than previously reported, and may have a negative impact on survival in horses with diarrhoea. Potential relevance: Results of blood cultures may be useful in formulating a prognosis for horses with diarrhoea. Further research is required to determine the effect of antimicrobial treatment on outcome.     

The microflora of the lower respiratory tract of the horse: an autopsy study

A series of 31 thoroughbreds and 18 non-thoroughbreds was examined post mortem to assess what bacteria might be present in the lower respiratory tract, and to assess their significance by correlating the bacteriological findings with histological changes in the lung. The distal trachea and seven representative lung sites were swabbed in each case. Sixty-six per cent of the sites were sterile with remaining sites producing scanty growths of mainly coagulase negative Staphylococcus spp., E. coli, Bacillus spp. and Pseudomonas spp. Anaerobes, mainly Clostridium perfringens, Bacteroides fragilis and Bacteroides oralis, were only recovered on enrichment media and were isolated more frequently from the right lung than the left. More bacterial species were isolated from thoroughbreds than non-thoroughbreds. Significant inflammation was absent in the majority of lungs examined and this correlated well with the large percentage of sterile sites and low number of potential pathogens. The results indicate that the lower respiratory tract of horses is normally sterile or may contain small numbers of bacteria of low pathogenicity. Chlamydia and respiratory viruses were not isolated from any horse.     

The effect of phenylbutazone on the plasma disposition of penicillin G in the horse

A pilot study in two ponies showed that the plasma concentrations of intramuscularly administered procaine penicillin were higher if phenylbutazone was administered concurrently. In two other trials, each involving five horses, intravenous sodium penicillin was administered with and without concurrent intravenously injected phenylbutazone, and procaine penicillin was injected intramuscularly with and without oral phenylbutazone. In both cases the plasma concentrations of penicillin were higher when phenylbutazone was given. The pharmacokinetic parameters indicated that the effect was probably due to a lower peripheral distribution because the penetration of penicillin into the tissues was greatly reduced.     

Peritonitis associated with Actinobacillus equuli in horses: 51 cases

OBJECTIVE: To review the clinical findings, diagnosis and treatment of 51 horses with peritonitis attributed to Actinobacillus equuli. DESIGN: Retrospective study of clinical cases. METHODS: Breed, age and gender of horse, history, physical examination findings, treatment and outcome were determined from the hospital records of 51 horses in which a diagnosis of peritonitis attributed to A. equuli was made between January 1993 and June 1999. Results of abdominal fluid cytology and bacteriology, antimicrobial sensitivity patterns, haematology and faecal egg counts, when performed, were also retrieved. RESULTS: There was a variety of breeds of horses affected. There were 35 male and 17 female horses, aged from 9 months to 22 years, presented. Lethargy, signs of depression with mild to moderate signs of abdominal pain and inappetence were the most common reasons for presentation. Most horses had elevated heart and respiratory rates, an elevated rectal temperature and reduced intestinal borborygmi heard on auscultation of the abdomen. Abnormal colour with an elevated protein were features of an abdominal fluid sample in 98% of horses and a marked elevation in nucleated cell count was present in all samples. Pleomorphic gram-negative rods were seen on cytology in 53% of samples and a positive culture of A. equuli was returned in 72% of samples. Other laboratory findings in some horses included mild haemoconcentration, hypoproteinaemia, an elevated circulating nucleated cell count with a left shift, an elevation in fibrinogen concentration and an elevated faecal egg count. All horses demonstrated a rapid response to treatment with procaine penicillin alone, or a combination of procaine penicillin and gentamicin sulphate. Where antimicrobial sensitivity tests were performed, all but two isolates were sensitive to procaine penicillin. All horses responded to antimicrobial and supportive therapy and were discharged from hospital. CONCLUSION: Horses with A. equuli peritonitis present with similar clinical signs as horses with other causes of abdominal pain. However, these signs, when evaluated in conjunction with the results of abdominal fluid analysis and response to treatment, are characteristic of A. equuli peritonitis. Pleomorphic gram-negative bacteria may be seen on a cytological preparation of the abdominal fluid sample, and a positive bacterial culture may be obtained in some, but not all, cases. Most isolates are sensitive to procaine penicillin, so treatment with procaine penicillin and gentamicin sulphate is recommended until antimicrobial sensitivity is known.     

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.     

Mechanisms of infection in the respiratory tract

Related to its potential vulnerability the respiratory tract has a very complex and effective defence apparatus. The interaction between these defence mechanisms and certain characteristics of aetiological agents results in a pattern in which initial infections by these agents tend to occur at specific sites in the tract. Infections in which the primary portal of entry is in the upper respiratory tract include Bordetella bronchiseptica and Haemophilus spp in pigs; Pasteurella spp in cattle, sheep, pigs; Mycoplasma spp in cattle, sheep, pigs and poultry; equine herpesvirus 1 in horses; infectious bovine rhinotracheitis in cattle; parainfluenza 3 in cattle and sheep; infectious laryngo-tracheitis and infectious bronchitis in poultry; feline viral rhinotracheitis and calicivirus in cats; Aujeszky's disease virus and swine influenza in pigs; and equine influenza in horses. Infections in which the primary portal of entry is in the lower respiratory tract include Aspergillus fumigatus in poultry and mammals, respiratory syncytial virus in cattle, distemper virus in dogs and adenovirus in cattle and dogs. A fuller understanding of the interactions between an agent and the host at the point of entry would make it much easier to develop effective vaccines and therapeutic agents.     

Pharmacokinetics of penicillin G procaine versus penicillin G potassium and procaine hydrochloride in horses

OBJECTIVE: To compare the pharmacokinetics of penicillin G and procaine in racehorses following i.m. administration of penicillin G procaine (PGP) with pharmacokinetics following i.m. administration of penicillin G potassium and procaine hydrochloride (PH). ANIMALS: 6 healthy adult mares. PROCEDURE: Horses were treated with PGP (22,000 units of penicillin G/kg of body weight, i.m.) and with penicillin G potassium (22,000 U/kg, i.m.) and PH (1.55 mg/kg, i.m.). A minimum of 3 weeks was allowed to elapse between drug treatments. Plasma and urine penicillin G and procaine concentrations were measured by use of high-pressure liquid chromatography. RESULTS: Median elimination phase half-lives of penicillin G were 24.7 and 12.9 hours, respectively, after administration of PGP and penicillin G potassium. Plasma penicillin G concentration 24 hours after administration of penicillin G potassium and PH was not significantly different from concentration 24 hours after administration of PGP. Median elimination phase half-life of procaine following administration of PGP (15.6 hours) was significantly longer than value obtained after administration of penicillin G potassium and PH (1 hour). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that i.m. administration of penicillin G potassium will result in plasma penicillin G concentrations for 24 hours after drug administration comparable to those obtained with administration of PGP Clearance of procaine from plasma following administration of penicillin G potassium and PH was rapid, compared with clearance following administration of PGP.