Concentrations of gentamicin in serum and bronchial lavage fluid after intravenous and aerosol administration of gentamicin to horses

OBJECTIVE: To compare concentrations of gentamicin in serum and bronchial lavage fluid after IV and aerosol administration of gentamicin to horses. ANIMALS: 9 healthy adult horses. PROCEDURE: Gentamicin was administered by aerosolization (20 ml of gentamicin solution [50 mg/ml]) and IV injection (6.6 mg of gentamicin/kg of body weight) to each horse, with a minimum of 2 weeks between treatments. Samples of pulmonary epithelial lining fluid were collected by small volume (30 ml) bronchial lavage 0.5, 4, 8, and 24 hours after gentamicin administration. Serum samples were obtained at the same times. All samples were analyzed for gentamicin concentration, and cytologic examinations were performed on aliquots of bronchial lavage fluid collected at 0.5, 8, and 24 hours. RESULTS: Gentamicin concentrations in bronchial lavage fluid were significantly greater 0.5, 4, and 8 hours after aerosol administration, whereas serum concentrations were significantly less at all times after aerosol administration, compared with IV administration. Neutrophil counts in bronchial lavage fluid increased from 0.5 to 24 hours, regardless of route of gentamicin administration. CONCLUSIONS AND CLINICAL RELEVANCE: Aerosol administration of gentamicin to healthy horses resulted in gentamicin concentrations in bronchial fluid that were significantly greater than those obtained after IV administration. A mild inflammatory cell response was associated with aerosol delivery of gentamicin and repeated bronchial lavage. Aerosol administration of gentamicin may have clinical use in the treatment of bacterial bronchopneumonia in horses.     

Bone gentamicin concentration after intra-articular injection or regional intravenous perfusion in the horse

Objective— To compare intra-articular (IA) and bone gentamicin concentrations achieved after intra-articular administration or regional intravenous perfusion (RIP).
Study Design— Experimental study.
Animals— Twelve healthy adult horses.
Methods— Horses were assigned to 2 treatment groups (  n = 6/group  ): Group 1, 1 g gentamicin administered simultaneously in both left and right metacarpophalangeal joints and group 2, 1 g gentamicin administered simultaneously in both left and right lateral palmar veins. Serum, synovial fluid, and bone biopsy specimens were collected. Gentamicin concentrations were determined by fluorescence polarization immunoassay. Bone, synovial fluid, and serum gentamicin concentrations were compared over time and between groups using 2-way ANOVA. Significance of all tests were evaluated at   P < .05  .
Results— IA metacarpophalangeal joint administration resulted in higher concentration of gentamicin in synovial fluid than RIP administration. Synovial fluid concentration remained above minimum inhibitory concentration (MIC) for common pathogens for over 24 hours with IA and RIP administration. Bone gentamicin concentration remained above MIC for 8 hours with both methods; there was no significant difference in gentamicin concentration in bone with either method. Neither IA nor RIP administration had a significant effect on serum concentration of gentamicin.
Conclusions— In normal horses, there is no difference in bone gentamicin concentration obtained with IA or RIP administration.
Clinical Relevance— Based on MIC for common equine pathogens, administration of gentamicin intra-articularly or by regional intravenous perfusion should be useful for treatment of osteomyelitis.     

Gentamicin concentrations in synovial fluid and joint tissues during intravenous administration or continuous intra-articular infusion of the tarsocrural joint of clinically normal horses

OBJECTIVE: To compare gentamicin concentrations achieved in synovial fluid and joint tissues during IV administration and continuous intra-articular (IA) infusion of the tarsocrural joint in horses. ANIMALS: 18 horses with clinically normal tarsocrural joints. PROCEDURE: Horses were assigned to 3 groups (6 horses/group) and administered gentamicin (6.6 mg/kg, IV, q 24 h for 4 days; group 1), a continuous IA infusion of gentamicin into the tarsocrural joint (50 mg/h for 73 hours; group 2), or both treatments (group 3). Serum, synovial fluid, and joint tissue samples were collected for measurement of gentamicin at various time points during and 73 hours after initiation of treatment. Gentamicin concentrations were compared by use of a Kruskal-Wallis ANOVA. RESULTS: At 73 hours, mean +/- SE gentamicin concentrations in synovial fluid, synovial membrane, joint capsule, subchondral bone, and collateral ligament of group 1 horses were 11.5 +/- 1.5 microg/mL, 21.1 +/- 3.0 microg/g, 17.1 +/- 1.4 microg/g, 9.8 +/- 2.0 microg/g, and 5.9 +/- 0.7 microg/g, respectively. Corresponding concentrations in group 2 horses were 458.7 +/- 130.3 microg/mL, 496.8 +/- 126.5 microg/g, 128.5 +/- 74.2 microg/g, 99.4 +/- 47.3 microg/g, and 13.5 +/- 7.6 microg/g, respectively. Gentamicin concentrations in synovial fluid, synovial membrane, and joint capsule of group 1 horses were significantly lower than concentrations in those samples for horses in groups 2 and 3. CONCLUSIONS AND CLINICAL RELEVANCE: Continuous IA infusion of gentamicin achieves higher drug concentrations in joint tissues of normal tarsocrural joints of horses, compared with concentrations after IV administration.     

Synovial fluid pH, cytologic characteristics, and gentamicin concentration after intra-articular administration of the drug in an experimental model of infectious arthritis in horses

Chemical and cytologic effects and bactericidal activity of gentamicin in septic synovial fluid were evaluated in an experimental model of infectious arthritis in horses. Septic arthritis was induced by inoculation of approximately 7.5 X 10(6) colony-forming units of Escherichia coli into 1 antebrachiocarpal joint in each of 16 clinically normal adult horses. Clinical signs of septic arthritis were evident 24 hours after inoculation. Horses were allotted to 3 groups: group-1 horses (n = 5) each were given 150 mg of gentamicin (50 mg/ml; 3 ml) intra-articularly (IA); group-2 horses (n = 5) each were given 2.2 mg of gentamicin/kg of body weight, IV, every 6 hours; and group-3 horses (n = 6) each were given buffered gentamicin, consisting of 3 mEq of sodium bicarbonate (1 mEq/ml; 3 ml) and 150 mg of gentamicin (50 mg/ml; 3 ml), IA. Synovial fluid specimens were obtained at posttreatment hour (PTH) 0, 0.25, 1, 4, 8, 12, and 24 via an indwelling intra-articular catheter. Synovial fluid pH was evaluated at PTH 0, 0.25, and 24. Microbiologic culture and cytologic examination were performed on synovial fluid specimens obtained at PTH 0 and 24, and gentamicin concentration was measured in all synovial fluid specimens. At PTH 0, E coli was isolated from synovial fluid specimens obtained from all horses. Synovial fluid pH was lower (range, 7.08 to 7.16) and WBC count was higher (range, 88,000 to 227,200 cells/microliters) and predominantly neutrophilic (95 to 99%) at PTH 0 than before inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adverse effects of gentamicin in scarlet macaws and galahs

The adverse effects of administration of gentamicin (5 mg/kg of body weight, IM, q 12 h) for 7 days were studied in healthy scarlet macaws (Ara macao) and galahs (Eolophus roseicapillus; cockatoos). Polydipsia and polyuria developed in each species, but were greater and persisted longer in the cockatoos. Peak water intake in the cockatoos more than quadrupled, and remained increased for 23 days after cessation of gentamicin administration. Plasma aspartate transaminase activity increased significantly (P less than 0.05) after treatment in the macaws, and plasma aspartate transaminase and lactate dehydrogenase activities increased in the cockatoos. Single IM administration of gentamicin (5 mg/kg) resulted in mean (+/- SEM) plasma concentration of 20.6 (+/- 1.85) micrograms/ml at 0.5 hour for either species of birds. There were no significant differences between mean plasma gentamicin concentrations for cockatoos and macaws at any time after drug administration, except at 12 hours, when values for cockatoos were significantly (P less than 0.05) greater than those for macaws. The elimination half-life for gentamicin after IM administration of 5 and 10 mg/kg was 1.17 and 1.07 hours, respectively, for macaws and 1.23 and 1.44 hours, respectively, for cockatoos. Correlation between drug disposition and adverse side effects could not be detected.     

Effect of gentamicin sulfate and sodium bicarbonate on the synovium of clinically normal equine antebrachiocarpal joints

The effect of gentamicin sulfate, unbuffered and buffered with sodium bicarbonate, on synovial fluid and membrane of clinically normal equine joints was evaluated. Thirty-six adult horses with clinically normal antebrachiocarpal joints were allotted to 6 treatment groups of 6 horses each. One antebrachiocarpal joint in each horse was chosen for treatment. Group-1 horses were given gentamicin (3 ml; 50 mg/ml); group-2 horses were given sodium bicarbonate (3 ml; 1 mEq/ml); group-3 horses were given gentamicin (3 ml; 50 mg/ml) and sodium bicarbonate (3 ml; 1 mEq/ml); group-4 horses were not treated; and horses of groups 5 and 6 were given polyionic physiologic solution (3 and 6 ml, respectively). Synovial fluid specimens were obtained from 5 horses of each group for cytologic analysis at postinjection hours (PIH) 0, 24, 72, and 192 and for pH determination at PIH 0, 0.25, 0.5, 1, 4, 8, 24, 72, and 192. The sixth horse of each group was euthanatized at PIH 24, and the synovial membrane of the treated and contralateral (nontreated) antebrachiocarpal joints was examined macroscopically and microscopically. After intra-articular gentamicin administration, the mean synovial fluid pH was lowest (5.98) at PIH 0.25, but by PIH 8, it was not significantly different from the control value (group-5 horses). When sodium bicarbonate was combined with gentamicin before intra-articular administration, the mean synovial fluid pH was lowest (7.07) at PIH 0.25, but by PIH 1, it was not significantly different from the control value (group-6 horses).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Regional limb perfusion for antibiotic treatment of experimentally induced septic arthritis.

Septic arthritis was induced in one antebrachiocarpal joint of seven horses by the intra-articular injection of 1 mL Staphylococcus aureus suspension containing a mean of 10(5) colony-forming units. Twenty-four hours after inoculation, four horses were treated by regional perfusion with 1 g of gentamicin sulfate, and three horses received 2.2 mg/kg gentamicin sulfate intravenously (IV) every 6 hours. Synovial fluid was collected for culture and cytology at regular intervals, and the synovial membranes were collected for culture and histologic examination at euthanasia 24 hours after the first treatment. Gentamicin concentration in the septic synovial fluid after three successful perfusions was 221.2 +/- 71.4 (SD) micrograms/mL; after gentamicin IV, it was 7.6 +/- 1.6 (SD) micrograms/mL. The mean leukocyte count in the inoculated joints decreased significantly by hour 24 in the successfully perfused joints. Terminal bacterial cultures of synovial fluid and synovial membranes were negative in two horses with successfully perfused joints. S. aureus was isolated from the infected joints in all three horses treated with gentamicin IV.     

Effect of intra-articular gentamicin sulfate on normal equine synovial membrane

Gentamicin sulfate (3 ml; 50 mg/ml) was administered intra-articularly into 30 normal equine radiocarpal joints after arthrocentesis. Arthrocentesis alone was performed on 10 normal radiocarpal joints. Synovial fluid evaluations and gross and microscopic examinations were performed on synovial fluid and synovial membrane of designated joints at selected daily intervals over a period of 10 days. Synovial fluid from gentamicin-injected joints had greater turbidity, higher RBC and WBC counts, and higher refractive indices than did joints not injected with gentamicin. The largest increases developed on days 1 or 2 after gentamicin injection, with mean total WBC, large mononuclear cell, small mononuclear cell, and polymorphonuclear cell counts of 23,860, 11,853, 857, and 11,150 cells/microliter, respectively. Arthrocentesis alone resulted in smaller increases in these counts. Microscopic changes seen in the synovial membrane of gentamicin-injected joints included edema, leukocytic infiltration, and loss of synovial lining cells. These inflammatory changes resolved within 7 days after gentamicin injection.     

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.     

Pharmacokinetics and body fluid and endometrial concentrations of cephapirin in mares

Six healthy adult horse mares were each given a single injection of sodium cephapirin (20 mg/kg of body weight, IV), and serum cephapirin concentrations were measured serially over a 6-hour period. The mean elimination rate constant was 0.78 hour-1 and the elimination half-life was 0.92 hours. The apparent volume of distribution (at steady state) and the clearance of the drug were estimated at 0.17 L/kg and 598 ml/hour/kg, respectively. Each mare was then given 4 consecutive IM injections of sodium cephapirin (400 mg/ml) at a dosage level of 20 mg/kg. Cephapirin concentrations in serum, synovial fluid, peritoneal fluid, CSF, urine, and endometrium were measured serially. After IM administration, the highest mean serum concentration was 14.8 micrograms/ml 25 minutes after the 4th injection. The highest mean synovial and peritoneal concentrations were 4.6 micrograms/ml and 5.0 micrograms/ml, respectively, 2 hours after the 4th injection. The highest mean endometrial concentration was 2.2 micrograms/g 4 hours after the 4th injection. Mean urine concentrations reached 7,421 micrograms/ml. Cephapirin did not readily penetrate the CSF. When cephapirin was given IM at the same dose, but in a less concentrated solution (250 mg/ml), serum concentrations peaked at 25.0 micrograms/ml 20 minutes after injection, but the area under the serum concentration-time curve was not significantly different (P greater than 0.05). The bioavailability of the drug was greater than or equal to 95% after IM injection.     

Single intravenous and multiple intramuscular dose pharmacokinetics and tissue residue profile of gentamicin in sheep

Single and multiple dose gentamicin regimens were compared in sheep to determine the relevant pharmacokinetic differences. Seven mature sheep were given 10 mg/kg of gentamicin by IV bolus. Serum concentrations were monitored for 19 days. Four weeks after the initial bolus, gentamicin was administered IM (3 mg/kg every 8 hours) for 7 days. Ewes were euthanatized and necropsied at 1, 8, and 15 days after termination of the IM regimen and the tissues were assayed for gentamicin. Serum concentrations were analyzed using a triexponential equation. The IV kinetic studies revealed an alpha half-life (t1/2) of 0.31 +/- 0.14 hours, beta t1/2 of 2.4 +/- 0.5 hours, and gamma t1/2 of 30.4 +/- 18.9 hours. Multiple IM dose kinetic studies revealed a beta t1/2 of 2.8 +/- 0.6 hours and gamma t1/2 of 82.1 +/- 17.8 hours. After multiple dosing, gamma t1/2 was significantly longer than after the single IV bolus (P less than 0.05). Twenty-four hour urine collection accounted for 75% to 80% of the total IV dose. Renal cortical gentamicin concentration reached 224 micrograms/g of tissue and then decreased, with a 90-hour t1/2. Renal medullary gentamicin concentration reached 18 micrograms/g with a 42-day t1/2. After multiple dosing, liver gentamicin concentration reached 11 micrograms/g and skeletal muscle concentrations were less than or equal to 0.6 micrograms/g. Route or duration of administration significantly affected the gamma-phase serum concentrations, which may influence gentamicin nephrotoxicosis. The present study also illustrated the complexities in predicting aminoglycoside withdrawal times for food-producing animals before slaughter.     

Pharmacokinetic and pathological evaluation of gentamicin in cats given a small intravenous dose repeatedly for five days.

Gentamicin was administered to six cats at a dosage of 3 mg/kg of body weight intravenously every 8 h for five days. Peak and trough serum gentamicin concentrations were measured after each injection. Gentamicin elimination rate and serum half-life were calculated. Serum urea nitrogen, creatinine, biochemistry profile, electrolyte, glucose, total protein, and albumin concentrations were measured daily. Urinalyses were performed before and after the five-day experimental period. The mean +/- SD peak serum gentamicin concentration was 7.19 +/- 1.10 micrograms/mL, and the trough concentration was 0.59 +/- 0.09 microgram/mL. These concentrations are known to be effective against most gentamicin-sensitive bacteria. The mean +/- SD gentamicin elimination rate was 0.0065 +/- 0.0004 min-1. The harmonic mean +/- pseudo standard deviation serum half-life of gentamicin was 107.21 +/- 12.79 min. There were no significant increases (P greater than 0.05) in clinicopathological variables. Microscopic examination of renal sections did not disclose pathological lesions. Signs of vestibular impairment were not observed. A dosage of 3 mg gentamicin/kg given intravenously every 8 h for five days was determined to be safe and to produce therapeutic blood levels in cats.     

Determination of synovial fluid and serum concentrations, and morphologic effects of intraarticular ceftiofur sodium in horses

OBJECTIVES: To determine the serum and synovial fluid concentrations of ceftiofur sodium after intraarticular (IA) and intravenous (IV) administration and to evaluate the morphologic changes after intraarticular ceftiofur sodium administration. STUDY DESIGN: Strip plot design for the ceftiofur sodium serum and synovial fluid concentrations and a split plot design for the cytologic and histopathologic evaluation. ANIMALS: Six healthy adult horses without lameness. METHODS: Stage 1: Ceftiofur sodium (2.2 mg/kg) was administered IV. Stage 2: 150 mg (3 mL) of ceftiofur sodium (pHavg 6.57) was administered IA into 1 antebrachiocarpal joint. The ceftiofur sodium was reconstituted with sterile sodium chloride solution (pH 6.35). The contralateral joint was injected with 3 mL of 0.9% sterile sodium chloride solution (pH 6.35). Serum and synovial fluid samples were obtained from each horse during each stage. For a given stage, each type of sample (serum or synovial fluid) was collected once before injection and 12 times after injection over a 24-hour period. All horses were killed at 24 hours, and microscopic evaluation of the cartilage and synovium was performed. Serum and synovial fluid concentrations of ceftiofur sodium were measured by using a microbiologic assay, and pharmacokinetic variables were calculated. Synovial fluid was collected from the active joints treated during stage 2 at preinjection and postinjection hours (PIH) 0 (taken immediately after injection of either the ceftiofur sodium or sodium chloride), 12, and 24, and evaluated for differential cellular counts, pH, total protein concentration, and mucin precipitate quality. RESULTS: Concentrations of ceftiofur in synovial fluid after IA administration were significantly higher (P = .0001) than synovial fluid concentrations obtained after IV administration. Mean peak synovial fluid concentrations of ceftiofur after IA and IV administration were 5825.08 microg/mL at PIH .25 and 7.31 microg/mL at PIH 4, respectively. Mean synovial fluid ceftiofur concentrations at PIH 24 after IA and IV administration were 4.94 microg/mL and .12 microg/mL, respectively. Cytologic characteristics of synovial fluid after IA administration did not differ from cytologic characteristics after IA saline solution administration. White blood cell counts after IA ceftiofur administration were < or =3,400 cells/ML. The mean synovial pH of ceftiofur treated and control joints was 7.32 (range, 7.08-7.5) and 7.37 (range, 7.31-7.42), respectively. Grossly, there were minimal changes in synovium or cartilage, and no microscopic differences were detected (P = .5147) between ceftiofur-treated joints and saline-treated joints. The synovial half-life of ceftiofur sodium after IA administration joint was 5.1 hours. CONCLUSIONS: Synovial concentrations after intraarticular administration of 150 mg of ceftiofur sodium remained elevated above minimal inhibitory concentration (MIC90) over 24 hours. After 2.2 mg/kg IV, the synovial fluid ceftiofur concentration remained above MIC no longer than 8 hours. CLINICAL RELEVANCE: Ceftiofur sodium may be an acceptable broad spectrum antimicrobial to administer IA in septic arthritic equine joints.     

Intramammary administration of gentamicin as treatment for experimentally induced Escherichia coli mastitis in cows.

In 8 Holstein cows, 50 colony-forming units (CFU) of Escherichia coli was administered into 1 mammary gland. Infections were established in all inoculated glands. In 4 of the 8 cows, 500 mg of gentamicin sulfate was administered by intramammary infusion 14 hours after inoculation; the other 4 cows were untreated controls. Infusions of gentamicin also were given after each of the 3 successive milkings after the initial infusion, so that a total dose of 2 g of gentamicin was given to each of the treated cows. During the 33-hour treatment period and for the first milking after the last infusion of gentamicin, the treated cows had a mean gentamicin concentration of greater than or equal to 31.0 micrograms/ml in milk samples that were collected from inoculated quarters immediately before each milking. Concentrations of 0.34 and 0.69 micrograms of gentamicin/ml were detected in milk from 2 cows at 8 days after inoculation with E coli. Mean serum concentrations of gentamicin were greater than or equal to 0.37 micrograms/ml throughout the treatment period and the first 12 hours after the last infusion, with a mean peak concentration of 0.96 micrograms/ml at 24.4 hours. The range of peak concentration of gentamicin detected in urine from all treated cows was 42 to 74.4 micrograms/ml. Peak concentration of E coli in milk in the treated cows (6.08 +/- 1.02 log10 CFU/ml) did not significantly (P greater than 0.05) differ from that of the control cows (5.26 +/- 1.00 log10 CFU/ml). Similarly, mean duration of infection in the treated cows (54 hours) did not differ significantly from that of the control cows (48 hours).(ABSTRACT TRUNCATED AT 250 WORDS)     

Bioavailability of gentamicin in dogs after intramuscular or subcutaneous injections

Healthy adult mixed-breed dogs, assigned to 2 groups of 6 dogs each, were given 3 mg of gentamicin sulfate/kg of body weight on 3 injection days 7 days apart. Group 1 was given gentamicin by rapid IV injection, by injection into the belly of the longissimus muscle at the first lumbar vertebrae (IM site 1), and by injection in the belly of the biceps femoris muscle (IM site 2). Group 2 was given gentamicin by rapid IV injection, by SC injection into the space over the cranial angle of the scapula on the midline (SC site 1), and by SC injection just caudal to the crest of the ilium (SC site 2). Pharmacokinetic values (mean +/- SD) from 12 dogs given gentamicin IV were 54.4 +/- 15.4 minutes for the effective half life, 2.29 +/- 0.48 ml/kg/min for clearance, and 172 +/- 25.4 ml/kg for volume of distribution at steady state. Bioavailability (93.92 to 96.65%) and peak plasma gentamicin concentration (9.43 to 10.89 micrograms/ml) were independent of injection site, but time to peak concentration when gentamicin was given at SC site 2 (43.33 minutes) was significantly (P less than 0.05) longer than that when gentamicin was given at IM site 1 (27.50 minutes). Absorption half-life was shorter after injections were given at both IM sites (8.9 and 9.8 minutes) than after injection was given at SC site 2 (18 minutes).     

Pharmacokinetics and synovial fluid concentrations of cephapirin in calves with suppurative arthritis

Six calves with suppurative arthritis were given a single IM injection of sodium cephapirin at a dosage of 10 mg/kg of body weight. Cephapirin concentrations were serially measured in serum and in normal and suppurative synovial fluid over a 24-hour period. Mean peak serum concentration was 6.33 microliters/ml at 20 minutes after injection. The highest cephapirin concentrations in normal and suppurative synovial fluid were 1.68 and 1.96 micrograms/ml, respectively, 30 minutes after injection. Overall mean cephapirin concentration in normal synovial fluid for the first 4 hours (1.04 +/- 0.612 micrograms/ml) was not significantly different from that in suppurative synovial fluid (0.88 +/- 0.495 micrograms/ml; P greater than 0.05). Elimination half-life was 0.60 hours and clearance was 1,593 ml/h/kg.     

Gentamicin sulfate in the horse: serum, synovial, peritoneal, and urine concentrations after single dose intramuscular administration

Ten healthy adult mares were given a single intramuscular dose (2.2 mg/kg) of gentamicin sulfate. Over a 48-h period, gentamicin concentrations were measured serially in the serum of all ten mares and in synovial fluid, peritoneal fluid, and urine of six of the mares. The mean peak serum gentamicin concentration was 5.73 μg/ml at 1 h. Gentamicin was detected in synovial fluid and peritoneal fluid, with mean peak gentamicin concentrations of 2.41 μg/ml and 3.92 μg/ml, respectively, observed at 2 h. These concentrations declined in parallel with serum concentrations and were not measurable at 48 h. Urine gentamicin concentration was relatively high, with a mean peak concentration of 424.9 μg/ml at 1 h after drug administration.     

Pharmacokinetics of gentamicin in cats given Escherichia coli endotoxin

Nineteen cats were given 3 mg of gentamicin sulfate/kg of body weight by rapid IV, SC, or IM injection for baseline values. Serum concentration of gentamicin vs time data were analyzed using a noncompartmental model based on statistical moment theory. One week later, each cat was given 0.5 microgram of Escherichia coli endotoxin/kg, IV. After cats had an increase in rectal temperature of at least 1 C, 3 mg of gentamicin/kg was administered by the same route used the previous week. Serum concentration of gentamicin vs time data were analyzed, and pharmacokinetic values were compared with base-line values. For IV studies, the half-life (t1/2) of gentamicin and the mean residence time were significantly different (P less than 0.05) compared with base line, whereas the total body clearance and apparent volume of distribution at steady state were not. The harmonic mean +/- pseudo SD for the t1/2 of gentamicin after IV administration was 76.8 +/- 12.6 minutes for base line and was 65.2 +/- 12.2 minutes in the same cats given endotoxin. The t1/2 of gentamicin after SC administration was 74.6 +/- 6.2 minutes for base line and was 65.2 +/- 13.6 minutes in the same cats given endotoxin. After IM administration, the t1/2 of gentamicin was 60.3 +/- 10 minutes for base line and was 59.7 +/- 13.6 minutes in the same cats given endotoxin. After IV administration of gentamicin, the arithmetic mean +/- SD for the mean residence time was 102.4 +/- 16.1 minutes for base line vs 79.2 +/- 18.4 minutes in the same cats given endotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of probenecid administration on cephapirin pharmacokinetics and concentrations in mares

Cephapirin (20 mg/kg of body weight, IV) was administered before and after 3 doses of probenecid (25, 50, or 75 mg/kg, intragastrically, at 12-hour intervals) to 2 mares. Clearance and apparent volume of distribution, based on area under the curve, were negatively correlated with probenecid dose. Clearance of cephapirin was decreased by approximately 50% by administration of 50 mg of probenecid/kg. Serum, synovial fluid, peritoneal fluid, CSF, urinary, and endometrial concentrations of cephapirin were determined after 5 doses of cephapirin (20 mg/kg, IM, at 12-hour intervals) without and with concurrently administered probenecid (50 mg/kg, intragastrically) to 6 mares, including the 2 mares given cephapirin, IV. Highest mean serum cephapirin concentrations were 16.1 +/- 2.16 micrograms/ml at 0.5 hour after the 5th cephapirin dose [postinjection (initial) hour (PIH) 48.5] in mares not given probenecid and 23.7 +/- 1.30 micrograms/ml at 1.5 hours after the 5th cephapirin dose (PIH 49.5) in mares given probenecid. Mean peak peritoneal fluid and synovial fluid cephapirin concentrations were 6.2 +/- 0.57 micrograms/ml and 6.6 +/- 0.58 micrograms/ml, respectively, without probenecid administration and 12.3 +/- 0.46 micrograms/ml and 10 +/- 0.78 micrograms/ml, respectively, with concurrent probenecid administration. Mean trough cephapirin concentrations for peritoneal and synovial fluids in mares given probenecid were 2 to 3 times higher than trough concentrations in mares not given probenecid. Overall mean cephapirin concentrations were significantly higher for serum, peritoneal fluid, synovial fluid, and endometrium when probenecid was administered concurrently with cephapirin (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)