Pharmacokinetics of gentamicin C1, C1a and C2 in horses after single intravenous dose

Gentamicin pharmacokinetics has not been studied in horses. Pharmacokinetics of gentamicin C1, C1a and C2 components following i.v. administration of total gentamicin at 6.6 mg/kg bwt to 6 healthy mature horses was determined. Significant differences in clearance, half-life (t 1/2), and mean residence time (MRT) between the gentamicin Cia and the 2 other components were found. The total body clearance (CL) of gentamicin C1a was 1.62 +/- 0.50 ml/min x kg and similar to the glomerular filtration rate (GFR) reported for horses. The CL of gentamicin C1 and C2 were 1.03 +/- 0.08 ml/min x kg and 1.10 +/- 0.15 ml/min x kg, respectively, and significantly slower than that of gentamicin C1a. The values of apparent volume of distribution at steady state were 0.22 +/- 0.05, 0.26 +/- 0.12 and 0.23 +/- 0.05 l/kg for gentamicin C1, C1a and C2, respectively. The MRT values were mean +/- s.d. 3.6 +/- 0.5, 2.7 +/- 0.3 and 3.5 +/- 0.4 h and the t 1/2 values were 3.1 (2.5-4.0), 2.4 (2.0-3.2) and 33 (2.4-4.3) h (harmonic mean and range) for gentamicin C1, C1a and C2, respectively. The MRT and t 1/2 values for gentamicin C1a were significantly shorter than those of gentamicin C1 and C2. It was concluded that the difference in pharmacokinetics between the gentamicin components has potential pharmacological and toxicological implications.     

Prediction of pharmacokinetic profiles of ampicillin sodium, gentamicin sulfate, and combination ampicillin sodium-gentamicin sulfate in serum and synovia of healthy horses

Pharmacokinetics of ampicillin sodium (11 mg/kg), gentamicin sulfate (2.2 mg/kg), and combination ampicillin sodium-gentamicin sulfate were determined for serum and synovia of healthy horses given single-dose IV injection and were not found to be different from those from other reports; however, a prolonged terminal gamma-phase for gentamicin (8,498 +/- 1,842 minutes) in serum of horses was found to exist. Pharmacokinetic interaction between combination ampicillin sodium-gentamicin sulfate was not observed int he serum or synovia. Prediction of ampicillin sodium or gentamicin sulfate concentrations in synovia, based on serum-based pharmacokinetics, cannot be accomplished solely upon analysis of peripheral-compartment pharmacokinetics. However, once equilibrium is achieved between synovia and extracellular fluid in the peripheral compartment, the decrease in drug concentrations in synovia parallels that in serum. Therefore, after 6 hours, synovial concentrations of gentamicin sulfate can be predicted based on peripheral-compartment pharmacokinetics, using an appropriate correction factor. The significance of these findings need to be correlated with clinical conditions so that a pharmacostatistical model for the prediction of synovial concentrations of drug(s) during treatment of horses with septic arthritis can be developed.     

Survival and complication rates in 300 horses undergoing surgical treatment of colic. Part 1: Short-term survival following a single laparotomy

REASONS FOR PERFORMING STUDY: A minority of equine colic cases prove fatal unless treated surgically; however, few studies have considered long-term survival and complication rates, and few have attempted to identify factors that might affect outcomes. Such information is required for owners and veterinary surgeons to make informed decisions about the most appropriate treatment for individual cases. OBJECTIVES: To document short-term survival rates of 300 horses undergoing colic surgery and analyse factors that might have predisposed to short-term death. METHODS: History, clinical and surgical findings, treatments and outcomes of 300 surgical colic cases (1994-2001) were reviewed. Comparisons among groups of discrete data were made using chi-squared or Student's t tests as appropriate. Significance was set at P < 0.05, and 95% confidence intervals were calculated for percentages. RESULTS: The short-term survival rate (to discharge) was 70.3% for all horses and 83.1% for those recovering from anaesthesia; for horses that had a single laparotomy it was 87.2%. The most common reasons for death/euthanasia in the post operative period after a single laparotomy were persistent pain/colic, post operative ileus and grass sickness. Horses with lesions involving the small intestine and caecum had lower survival rates (75.2 and 66.7%, respectively) than those with large colon or small colon lesions (89.9 and 100%, respectively). The survival rate for ischaemic/strangulating lesions (68.9%) was lower than for simple obstructions (90.5%). CONCLUSIONS: Short-term survival of horses undergoing exploratory laparotomy for acute colic is dependent on many factors, including the nature of the underlying disease, cardiovascular status and post operative complications. POTENTIAL RELEVANCE: These retrospective studies may be used as a basis for prospective studies assessing treatments that could ultimately improve survival and decrease complication rates.     

Multiple once-daily dose pharmacokinetics and renal safety of gentamicin in dogs

In this study the pharmacokinetics and renal safety of gentamicin in healthy dogs was investigated after multiple dosing. Six adult male dogs received once-daily gentamicin (6 mg/kg) intramuscularly for 5 days. Serial blood samples were taken on days 1 and 5 of treatment, and at predose, 1 and 6 h on days 2, 3 and 4. Urinalysis, hematology and serum biochemistry evaluation were carried out before, 7 and 14 days after the first gentamicin administration. Mean value of the main pharmacokinetic parameters were: AUC (microg.h/mL), 97.4 and 100.2; terminal half-life (harmonic mean), 0.76 and 1.01 h; ClB/F (mL/min.kg), 1.24 and 1.10; VD(area)/F (L/kg), 0.084 and 0.10; MRT (h), 1.48 and 1.77; Cmax (microg/mL), 54.5 and 49.2; tmax (h), 0.40 and 0.48 for the first and last dose, respectively. Accumulation was determined as R1 = 0.97 and R2 = 1.22. Mean trough gentamicin serum concentrations were 0.06, 0.07, 0.09, 0.1 and 0.1 microg/mL for the first, second, third, fourth and fifth dose, respectively. Statistically significant increases (P < 0.05) were found for last dose MRT and fourth and fifth trough gentamicin serum concentrations. Laboratory tests detected a slight increase in serum creatinine and urea nitrogen concentrations (one dog), decreased specific urine gravity (one dog) and presence of few granular casts (two dogs). It is concluded that once-daily administration of gentamicin may provide adequate serum levels to treat most susceptible gram-negative infections with little or no nephrotoxicity in dogs.     

LAPAROTOMY IN EQUINE COLIC—A REPORT OF THIRTEEN CLINICAL CASES

A report of 13 unselected clinical cases of colic in horses which were submitted to laparotomy is presented, together with one case of experimental end-to-side anastomosis of the ileum into the caecum. Cases are divided into acute or peracute with diverse aetiology, and subacute or chronic where all the lesions involved the small intestine. The technique of anaesthesia and surgical procedures is described and emphasis is placed on the necessity of adequate fluid therapy in such cases.     

Pharmacokinetics of single doses of gentamicin given intravenously and intramuscularly to turkeys

The disposition and absorption kinetics of gentamicin were studied in healthy, mature male and female turkeys (n = 10). Single doses of gentamicin (5 mg/kg) were injected either i.v. or i.m. with a 30-day rest period between each treatment. Baseline and serial venous blood samples (n = 17) were collected from each turkey. Serum concentrations of gentamicin were determined in duplicate for 24 h after each treatment, using radio-immunoassay. Using nonlinear least-square regression methods, the combined data of the i.v. and i.m. treatments were best described by a two-compartment open model. Kinetic analysis of the data after a single i.v. dose provided the following mean values: t1/2 alpha = 0.170 +/- 0.093 h, t1/2 beta = 2.57 +/- 0.79 h, MRT = 3.62 +/- 0.96 h, Vc = 0.090 +/- 0.017 l/kg, Vd(ss) = 0.172 +/- 0.024 l/kg, Vd(area) = 0.190 +/- 0.030 l/kg, and Clt = 49.8 +/- 9.8 ml/h/kg. After a single i.m. dose, the following mean values were determined: MRT = 5.10 +/- 1.73 h, t1/2abs = 0.74 +/- 0.66 h, tlag = 0.07 +/- 0.19 h, Clt/F = 50.7 +/- 12.5 ml/h/kg, Vd(area)/F = 0.193 +/- 0.044 l/kg, and F = 102 +/- 21%. Kinetic calculations made with the single i.m. data predicted that an i.m. injection of gentamicin at the dosage rate of 3 mg/kg q. every 12 h would provide average steady state serum concentrations of 4.93 micrograms/ml.     

Primary gastric impaction in horses: A retrospective study of 20 cases (2005–2008)

Primary gastric impaction is an uncommon condition. Furthermore, the factors associated with gastric impaction and the optimal method of treatment are not clear. The aim of this article is to describe the clinical findings, treatment and outcome of horses with a primary gastric impaction. Medical records of horses that presented with a primary gastric impaction between 2005 and 2008 were reviewed and 20 horses with a primary gastric impaction identified. Diagnosis of a primary gastric impaction was made if the horse had been fasted for a minimum of 16 h, a concretion of ingesta precluded visualisation of the margo plicatus and there was no evidence of concurrent intestinal pathology. Thirteen of 20 (65%) horses were presented on an emergency basis. The most common complaint was inappetence (50%) followed by acute colic (35%) and recurrent colic (35%). On initial examination for colic, all horses had a normal heart rate and 7 of 20 (35%) had decreased gastrointestinal borborygmi. All horses were treated with enteral fluid therapy. The median dose of fluids administered per day was 5 doses (range 1–8 doses) of 2–10 l of isotonic electrolyte solution. The median length of treatment until resolution was 2 days (range 1–5 days). Eighteen of 20 (90%) horses survived to discharge. Primary gastric impaction appears to be a condition with clinical signs of inappetence and mild abdominal discomfort. This is the largest group of horses reported that were treated with enteral fluid therapy for a gastric impaction and it was concluded that enteral fluid therapy was of value in this study.     

Gentamicin pharmacokinetics in diabetic dogs

Reduction of the prolonged terminal elimination phase of gentamicin may be caused by diabetes mellitus, irrespective of the model of diabetes. To test this hypothesis, five normal dogs, three dogs with alloxan-induced diabetes mellitus, and four dogs with naturally occurring diabetes mellitus (all of which were given exogenous insulin to control hyperglycemia) were given 4.4 mg/kg gentamicin intravenously. Serum pharmacokinetics were analyzed using non-compartmental pharmacokinetics assuming a sum of exponential terms. Gentamicin pharmacokinetics during the first 8 h were the same in normal and diabetic dogs. Over 7 days, MRT in normal dogs (5830 +/- 2970 min, mean +/- SD) was longer (P less than 0.01) than in diabetic dogs (136 +/- 164 min). In diabetic dogs, Cls was greater (3.01 +/- 0.86 ml/min/kg) than in normal dogs (1.45 +/- 0.11 ml/min/kg; P less than 0.01), whereas Vd(ss) was smaller in diabetic dogs (0.405 +/- 0.508 l/kg) than in normal dogs (8.56 +/- 4.48 l/kg; P less than 0.01). Serum gentamicin concentrations were less than 0.020 microgram/ml by 2 days in all of the diabetic dogs, but were 0.048 +/- 0.018 microgram/ml at 7 days in normal dogs. Thus, diabetes mellitus, either induced by alloxan administration or naturally occurring, abolished the terminal elimination phase of gentamicin disposition in a non-rodent species.     

Pharmacokinetic adjustment of gentamicin dosing in horses with sepsis

Serum gentamicin concentrations were measured and pharmacokinetic values were calculated for 12 equine patients receiving parenteral gentamicin therapy. Horses were selected for monitoring of gentamicin pharmacokinetics if they met several criteria of high risk for gentamicin-induced toxicosis. Two blood samples were obtained, one immediately before gentamicin dosing and one at 1 hour after dosing. Gentamicin serum concentrations were analyzed and dosage adjustments were made on the basis of calculated one-compartment pharmacokinetic values. Nine of the 12 horses required dosage adjustment to optimize therapeutic concentrations. Even for horses for which there was no evidence of decreased renal function, variation in the disposition of gentamicin was substantial. Because of the larger volume of distribution in foals, an initial dosage of 3 mg/kg every 12 hours was found to best approximate target concentrations. Therefore, published standard dosages were a poor means of achieving desired peak and trough concentrations in many animals. Seemingly, for optimal treatment of horses with sepsis, gentamicin dosage adjustments based on the patient's pharmacokinetic values is required.     

Are horses that undergo an exploratory laparotomy for correction of a right dorsal displacement of the large colon predisposed to post operative colic,compared to other forms of large colon displacement?

Reason for performing study: It is a clinical impression that horses diagnosed with a right dorsal displacement (RDD) of the large colon, are more likely to suffer from recurrent episodes of colic post operatively, compared to other forms of nonstrangulating large colon displacement. Objectives: To investigate whether the type of nonstrangulating large colon displacement identified at exploratory laparotomy would influence long‐term outcome. Hypothesis: Horses identified with a RDD of the large colon at exploratory laparotomy would be more likely to experience recurrent episodes of post operative colic than other types of displacement. Materials and methods: Medical records for horses undergoing an exploratory laparotomy, from 2000–2008, for a nonstrangulating large colon displacement were reviewed. Data retrieved included: subject details, previous medical history, details of current episodes of colic, results of preoperative examination, surgical findings and procedures, post operative management and complications. Follow‐up information was obtained by reference to computerised clinical records and by telephone questionnaire administered to the horse's owner or carer, and included details of any colic episodes exhibited by the horse after discharge and whether a repeat celiotomy had been required to resolve the colic episodes. Results: There were 165 surgeries identified, in 154 horses. It was found that those horses with RDD were significantly more likely to experience recurrent episodes of colic requiring veterinary intervention post operatively compared to other types of displacement. Clinical relevance: Long‐term prognosis and likelihood of post operative complications is an important consideration for both owners and veterinarians.     

Multiple oral dosing of ketoconazole influences pharmacokinetics of quinidine after intravenous and oral administration in beagle dogs

In this study, we investigated the effect of multiple oral dosing of ketoconazole (KTZ) on pharmacokinetics of quinidine (QN), a CYP3A substrate with low hepatic clearance, after i.v. and oral administration in beagle dogs. Four dogs were given p.o. KTZ for 20 days (200 mg, b.i.d.). QN was administered either i.v. (1 mg/kg) or p.o. (100 mg) 10 and 20 days before the KTZ treatment and 10 and 20 days after start of KTZ treatment. Multiple oral dosing of KTZ decreased significantly alpha and beta, whereas increased t(1/2beta), V(1), and k(a). The KTZ treatment also decreased significantly both total body clearance (Cl(tot)) and oral clearance (Cl(oral)). No significant change in bioavailability was observed in the presence of KTZ. Co-administration of KTZ increased C(max) of QN to about 1.5-fold. Mean resident time after i.v. administration (MRT(i.v.)), and after oral administration (MRT(p.o.)) of QN were prolonged to about twofold, whereas mean absorption time (MAT) was decreased to 50%. Volume of distribution at steady state (V(d(ss))) of QN was unchanged in the presence of KTZ. These alterations may be because of a decrease in metabolism of QN by inhibition of KTZ on hepatic CYP3A activity. In conclusion, multiple oral dosing of KTZ affected largely pharmacokinetics of QN after i.v. and oral administration in beagle dogs. Therefore, KTZ at a clinical dosing regimen may markedly change the pharmacokinetics of drugs primarily metabolized by CYP3A with low hepatic clearance in dogs. In clinical use, much attention should be paid to concomitant administration of KTZ with the drug when given either p.o. or i.v.     

Evaluation of Equine Albumin Solution in Fluid Therapy in Horses with Colic

Equine albumin solution can be a good therapeutic option in fluid replacement for treatment of horses with colic. The purpose of this study was to evaluate the effects of initial fluid therapy with equine albumin solution in horses presenting with colic and mild-to-moderate dehydration, and to compare this therapy with fluid therapy based on crystalloids alone. Nineteen horses of both genders presenting with colic and mild-to-moderate dehydration were used. Animals were randomly assigned to one of two groups (control: fluid therapy based on crystalloid solutions; experimental: fluid therapy based on equine albumin and crystalloid solutions). Physical examination, hematocrit determination, blood gas analysis, serum biochemistry, blood and peritoneal lactate assessment, and measurement of colloid osmotic and arterial pressure were performed at predetermined times. Good results were obtained with equine albumin solution. More fluid is attracted into and maintained in the intravascular compartment, despite infusion of small volumes, as indicated by higher arterial pressure, lower capillary refill time, lower hematocrit and serum protein concentrations, lower colloid osmotic pressure, and better skin turgor. Equine albumin solution has good oncotic action and is a safe fluid therapy option for horses with colic and mild-to-moderate dehydration. Our results suggest it can be a good choice of fluid for correction of severe dehydration, although further research is necessary to determine the adequate dose in such cases.     

Comparison of serum and renal gentamicin concentrations with fractional urinary excretion tests as indicators of nephrotoxicity

Gentamicin was given to six sheep at a dosage rate of 80 mg/kg/day divided into three daily doses to cause nephrotoxicity. Peak serum gentamicin concentrations rose significantly throughout dosing (P less than 0.05), but trough serum gentamicin concentrations increased dramatically (P less than 0.01) from initial concentrations of 3.2-9.1 micrograms/ml to final trough concentrations of 31.5-195 micrograms/ml by 6-10 days on gentamicin. The serum gentamicin elimination half-life (t1/2) was doubled in each animal by approximately 6 days on therapy, with the sheep that were the most clinically affected by the nephrotoxic effects of gentamicin showing increases in t1/2 earlier than those sheep that remained less intoxicated. These changes occurred before many other clinical indicators of nephrotoxicity, with only urinary enzyme excretions preceding the changes in gentamicin elimination. Thus, alterations in the elimination of gentamicin may be one of the first clinical indicators of the occurrence of gentamicin-induced nephrotoxicity.     

Removal of a fragmented nasogastric tube from the transverse colon of a horse undergoing exploratory celiotomy for colic

This report describes the clinical course and surgical findings of a 5-year-old Warmblood gelding referred for colic with a previous history of intermittent colic episodes, and gastric ulcers diagnosed by gastroscopy in the preceding months. The horse underwent medical treatment but remained painful and surgery was elected. The horse underwent an exploratory laparotomy during which an impaction was identified in the transverse colon that was associated with an approximately 1 metre segment of nasogastric tube. The foreign body was removed via an enterotomy in the left dorsal colon, and the horse recovered well from surgery. No complications were encountered post-operatively.     

Survival and complication rates in 300 horses undergoing surgical treatment of colic. Part 2: Short-term complications

REASONS FOR PERFORMING STUDY: Few studies have assessed short- and long-term complication rates of horses following surgical treatment of colic, a potentially fatal condition. Complications can lead to patient discomfort and increased costs; knowledge of predisposing factors may help to reduce complication rates. OBJECTIVES: To document and analyse short-term complications in 300 horses undergoing colic surgery, and to assess some of the possible predisposing factors. METHODS: History, clinical findings, surgical findings and procedures, and post operative treatments of 300 consecutive surgical colic cases (1994-2001) were reviewed. Comparisons among groups of discrete data were made using chi-squared or Student's t tests as appropriate. RESULTS: Short-term complications in 227 horses following a single laparotomy included colic/pain (28.2%), incisional drainage or infection (26.9%), post operative ileus (13.7%), severe endotoxaemic shock (12.3%), jugular thrombophlebitis (7.5%), septic peritonitis (3.1%) and colitis/diarrhoea (2.2%). Horses with small bowel obstruction had a higher rate of post operative ileus than those with large bowel obstruction. Rates of post operative pain and shock were higher in horses with small colon rather than large colon obstruction, and in those that had an ischaemic rather than a simple obstruction. The rate of wound complications increased with increasing total plasma protein concentration at admission. Horses that had a repeat laparotomy had a higher rate of wound complications compared to those that had a single laparotomy. Application of a stent bandage was associated with a higher rate of wound complications than if no stent was applied; however, application of an incise drape over the wound for recovery was associated with a lower rate of wound complications than for horses that had no protective covering of the wound. CONCLUSIONS: The most common short-term post operative complications following colic surgery were pain, incisional drainage, ileus, endotoxaemiac shock and jugular thrombophlebitis. Some factors that appeared to predispose to these complications were identified. Although many of these factors related to the underlying disease process, a number of factors, including surgical techniques, were identified that might be amenable to modification. POTENTIAL RELEVANCE: Prospective studies to assess the effects of modifying these factors on survival rates should be performed.     

Comparative disposition kinetics and plasma protein binding of gentamicin sulphate in three juvenile animal species

The pharmacokinetics of gentamicin was studied in lambs, calves and foals, respectively after single intravenous (i.v.) injections of 5 mg kg(-1) body weight. The plasma concentration-time curves of gentamicin sulphate were best fitted to follow a two-compartment open model in calves and foals and a three-compartment open model in lambs. Gentamicin showed high plasma level at 5 min post-injection. Then its concentration decreased gradually until its minimum detectable level at 10 and 12 h post-injection in foals and calves, respectively, was reached. In contrast, the plasma concentrations were much higher in lambs and persisted up to 48 h from the onset of injection. Values of pharmacokinetic parameters for gentamicin sulphate in different animals after i.v. injections were calculated. Pharmacokinetic data in lambs demonstrated a triphasic decline in plasma gentamicin concentration with slow terminal elimination phase (washout phase) with (t(1/2y)) of 7.7 h. Gentamicin showed a small volume of distribution Vd(ss) (80.3 ml kg(-1)) in lambs indicating that the drug is slightly distributed in extra-vascular tissues. The overall rate of total body clearance ClB in lambs was (0.46 ml kg(-1)) slower than in calves (1.5 ml kg(-1)) and foals (2.7 ml kg(-1)). In vitro protein binding per cent of gentamicin sulphate in plasma were 16.80, 11.03 and 7.98% in lambs, calves and foals. The results of this study emphasize the importance of determining the pharmacokinetics of gentamicin in each species of young animals separately.     

Survey of complications and antimicrobial use in equine patients at veterinary teaching hospitals that underwent surgery because of colic

OBJECTIVE: To determine current practices regarding use of antimicrobials in equine patients undergoing surgery because of colic at veterinary teaching hospitals. DESIGN: Survey. SAMPLE POPULATION: Diplomates of the American College of Veterinary Surgeons performing equine surgery at veterinary teaching hospitals in the United States. PROCEDURE: A Web-based questionnaire was developed, and 85 surgeons were asked to participate. The first part of the survey requested demographic information and information about total number of colic surgeries performed at the hospital, number of colic surgeries performed by the respondent, and whether the hospital had written guidelines for antimicrobial drug use. The second part pertained to nosocomial infections. The third part provided several case scenarios and asked respondents whether they would use antimicrobial drugs in these instances. RESULTS: Thirty-four (40%) surgeons responded to the questionnaire. Respondents indicated that most equine patients undergoing surgery because of colic at veterinary teaching hospitals in the United States received antimicrobial drugs. Drugs that were used were similar for the various hospitals that were represented, and for the most part, the drugs that were used were fairly uniform irrespective of the type of colic, whereas the duration of treatment varied with the type of colic and the surgical findings. The combination of potassium penicillin and gentamicin was the most commonly used treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study document the implementation of recommendations by several authors in veterinary texts that antimicrobial drugs be administered perioperatively in equine patients with colic that are undergoing surgery. However, the need for long-term antimicrobial drug treatment in equine patients with colic is unknown.     

Postoperative pharmacokinetics of meloxicam in horses after surgery for colic syndrome

NSAID s are often used in horses with colic syndrome during the postoperative period, due to their ability to contrast endotoxemia and to promote an analgesic and anti‐inflammatory effect. As the pharmacokinetics of a drug are often modified in unhealthy animals compared to healthy subjects, the aim of this study was to evaluate the pharmacokinetic profile of meloxicam after i.v. administration in horses undergoing laparotomy for colic syndrome. Eight horses received 0.6 mg/kg of meloxicam i.v. towards the end of surgery. Blood samples were taken at scheduled time points during the following 24 hr. The serum concentration of the drug was determined by HPLC . Terminal half‐life (6.88 ± 2.96 hr), volume of distribution at steady‐state (186.53 ± 61.20 ml/Kg) and clearance (27.91 ± 5.72 ml kg^?1 hr^?1) were similar to those reported in literature for healthy horses. This result suggests that no adjustment of the approved dose should be necessary when meloxicam is used to treat horses in the immediate postoperative period after surgery for colic syndrome.     

Continuous infusion of gentamicin into the tarsocrural joint of horses

OBJECTIVE: To develop a method for continuous infusion of gentamicin into the tarsocrural joint of horses, to determine pharmacokinetics of gentamicin in synovial fluid of the tarsocrural joint during continuous infusion, and to evaluate effects of continuous infusion of gentamicin on characteristics of the synovial fluid. ANIMALS: 12 healthy adult horses. PROCEDURE: An infusion catheter consisting of flow control tubing connected to a balloon infuser was used. Gentamicin solution (100 mg/ml) was infused in the right tarsocrural joint and balanced electrolyte solution was infused in the left tarsocrural joint for 5 days. Synovial fluid and serum gentamicin concentrations were measured by use of a fluorescence polarization immunoassay. RESULTS: 17 of the 24 (71%) infusion catheters initially placed functioned without complications for the entire 5-day infusion period. Median gentamicin concentration in synovial fluid from treated joints during the 5-day infusion period ranged from 2875 to 982 microg/ml. Median serum gentamicin concentration during this period ranged from 2.31 to 2.59 microg/ml. Mean (+/- SD) elimination half-life and total clearance of gentamicin from the synovial fluid were 6.25+/-1.01 hours and 1.52+/-0.96 ml/min, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: An infusion catheter can be used for continuous infusion of gentamicin into the tarsocrural joints of horses for up to 5 days. At a gentamicin dosage of 0.17+/-0.02 mg/kg/h, continuous intra-articular infusion results in synovial fluid gentamicin concentrations greater than 100 times the minimal inhibitory concentration reported for common equine pathogens.