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)     

Serum concentrations of gentamicin in cats

Twenty-one adult cats, allotted into 2 groups, were given gentamicin sulfate at dosages of either 5.0 mg/kg of body weight or 2.5 mg/kg as a single IM injection. During a 24-hour period, serum concentrations of gentamicin were measured serially, using a fluorescence immunoassay. The mean peak serum concentration of gentamicin in cats given 5.0 mg/kg was 23.1 micrograms/ml at postinjection hour (PIH) 0.5; thereafter, the mean serum concentration steadily decreased to 2.0 micrograms/ml at PIH 24. The mean peak serum concentration for cats administered 2.5 mg/kg was 9.1 micrograms/ml at PIH 0.5; thereafter, the mean serum concentration steadily decreased to 1.3 micrograms/ml at PIH 12. Serum therapeutic concentrations, without exceeding toxic concentrations, were attained at the 2.5 mg/kg dosage.     

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.     

Pharmacokinetics of single-dose intravenous or intramuscular administration of gentamicin in roosters

Healthy mature roosters (n = 10) were given gentamicin (5 mg/kg of body weight, IV) and, 30 days later, another dose IM. Serum concentrations of gentamicin were determined over 60 hours after each drug dosing, using a radioimmunoassay. Using nonlinear least-square regression methods, the combined data of IV and IM treatments were best fitted by a 2-compartment open model. The mean distribution phase half-life was 0.203 +/- 0.075 hours (mean +/- SD) and the terminal half-life was 3.38 +/- 0.62 hours. The volume of the central compartment was 0.0993 +/- 0.0097 L/kg, volume of distribution at steady state was 0.209 +/- 0.013 L/kg, and the total body clearance was 46.5 +/- 7.9 ml/h/kg. Intramuscular absorption was rapid, with a half-life for absorption of 0.281 +/- 0.081 hours. The extent of IM absorption was 95 +/- 18%. Maximal serum concentration of 20.68 +/- 2.10 micrograms/ml was detected at 0.62 +/- 0.18 hours after the dose. Kinetic calculations predicted that IM injection of gentamicin at a dosage of 4 mg/kg, q 12 h, and 1.5 mg/kg, q 8 h, would provide average steady-state serum concentrations of 6.82 and 3.83 micrograms/ml, with minimal steady-state serum concentrations of 1.54 and 1.50 micrograms/ml and maximal steady-state serum concentrations of 18.34 and 7.70 micrograms/ml, respectively.     

Plasma and synovial fluid concentrations of gentamicin in horses after intra-articular administration of buffered and unbuffered gentamicin

The concentration of gentamicin in plasma and synovial fluid of normal adult horses was measured periodically for 24 hours after IV (2.2 mg/kg of body weight), intra-articular (IA; 150 mg), and simultaneous IV and IA administrations. Gentamicin also was buffered with sodium bicarbonate (3 mEq) and then was administered IA and simultaneously IV and IA. Synovial fluid specimens were obtained via an indwelling catheter placed into the antebrachiocarpal joint. The peak mean plasma gentamicin concentration (8.30 micrograms/ml) after IV administration was significantly (P less than 0.05) greater than that (0.69 microgram/ml) after IA administration of gentamicin and that (0.55 microgram/ml) after administration of gentamicin buffered with sodium bicarbonate. Gentamicin concentration greater than a therapeutic concentration was not attained in the plasma after IA administration of buffered or unbuffered gentamicin. The peak mean synovial fluid concentration (1,828 micrograms/ml) after IA administration of unbuffered gentamicin was significantly (P less than 0.05) greater than that (2.53 micrograms/ml) after IV administration and significantly (P less than 0.05) less than that (5,720 micrograms/ml) after simultaneous IV and IA administration. The peak mean synovial fluid concentration after IA administration of buffered gentamicin, with and without simultaneous IV administration (2,128 and 2,680 micrograms/ml, respectively), was not significantly different than that after IA treatment with unbuffered gentamicin. Mean synovial fluid concentration did not differ significantly between groups after IA administration of gentamicin in any combination at postinjection hours 8, 12, and 24, but remained significantly (P less than 0.05) greater than that at the same times after IV administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dose-dependent pharmacokinetics of gentamicin in sheep

Dose-related changes in the pharmacokinetics of gentamicin sulfate were investigated in 9 sheep given 3, 10, or 20 mg/kg of body weight IV in a crossover design with a 24-day washout period. The pharmacokinetics of the 3 mg/kg single dose were compared with that of the terminal phase pharmacokinetics of 3 mg of gentamicin/kg IV every 8 hours for 7 days in 8 additional sheep. Serum concentrations were monitored for 21 to 24 days after the dose. Polyexponential equations were fit to each data set. The number of exponential terms was determined by optimizing the fit for each data set. The pharmacokinetics of the 3 mg/kg single dose were mainly described by triexponential equations. The 10 mg/kg and the 20 mg/kg single doses and the 3 mg/kg multiple-dose data were described by a tetraexponential equation. The elimination rate constant was significantly smaller (P less than 0.05) after the larger single doses, and the serum gentamicin clearance increased as the dose increased (P less than 0.05). The crossover design sequence had a significant effect on serum gentamicin clearance and the area under the curve normalized to unit dose (P less than 0.01). The final exponential phase was not detectable with the present assay sensitivity under the 3 mg/kg single dose. The triexponential equation underpredicted the terminal serum concentrations determined after the 3 mg/kg multiple dose, whereas the 4 phase equation overpredicted the same terminal serum concentrations, perhaps reflecting saturation of the tissue pools that were mirrored by the serum gentamicin concentrations after 24 hours. The present study emphasized the complexity of the terminal phase gentamicin. pharmacokinetics and acknowledged the need for a long-term washout period when using the crossover design for gentamicin pharmacokinetic studies.     

Effects of ketanserin on pulmonary hemodynamics, lung mechanics, and gas exchange in endotoxemic pigs

The effects of ketanserin on pulmonary hemodynamics, lung mechanics, and gas exchange were determined in anesthetized 10- to 14-week-old pigs after they were endotoxemic for 1 or 4.5 hours. Saline solution was given to controls (group 1). Escherichia coli endotoxin (055-B5) was infused IV at a dosage of 5 micrograms/kg for 1 hour (group 2). In group 3, endotoxin was infused at 5 micrograms/kg the first hour plus a continuous infusion of endotoxin at 2 micrograms/kg/hr. Ketanserin, a specific serotonin receptor antagonist, was infused IV (300 micrograms/kg) after pigs were endotoxemic for 1 or 4.5 hours (groups 2 and 3, respectively). At 1 hour of endotoxemia, mean pulmonary artery pressure and pulmonary vascular resistance were increased, and cardiac index was decreased. Ketanserin caused a small attenuation of the increases in mean pulmonary artery pressure and pulmonary vascular resistance, indicating that serotonin may have a small role in the endotoxin response at 1 hour. At 4.5 hours of endotoxemia, mean pulmonary artery pressure, pulmonary vascular resistance, alveolar dead space ventilation, and alveolar-arterial oxygen gradient were increased, and cardiac index and lung dynamic compliance were decreased; ketanserin significantly attenuated the endotoxin-induced changes in cardiac index, mean pulmonary artery pressure, pulmonary vascular resistance, and lung dynamic compliance. Ketanserin also decreased the blood temperature after pigs were endotoxemic for 4.5 hours. However, the endotoxin-induced increases (at 4.5 hours) in alveolar-arterial oxygen gradient and alveolar dead space ventilation were not acutely reversed by ketanserin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Drug disposition and dosage determination of once daily administration of gentamicin sulfate in horses after abdominal surgery.

OBJECTIVE: To evaluate pharmacokinetics of once daily i.v. administration of gentamicin sulfate to adult horses that had abdominal surgery. DESIGN: Prospective study. ANIMALS: 28 adult horses that underwent abdominal surgery for colic. PROCEDURE: 14 horses were treated with each dosage of gentamicin (i.e., 6.6 or 4 mg/kg, i.v., q 24 h) and blood samples were collected for pharmacokinetic analysis. Plasma gentamicin concentrations were measured by use of a fluorescence polarization immunoassay. Pharmacokinetic analysis measured the elimination half-life, volume of distribution, and gentamicin total systemic clearance. Treatment outcome, CBC, and serum creatinine concentrations were recorded. RESULTS: 1 horse in the high-dosage group died. All other horses successfully recovered, and did not develop bacterial infection or have evidence of drug toxicosis resulting in renal injury. Mean pharmacokinetic variables for gentamicin administration at a high or low dosage (i.e., 6.6 or 4 mg/kg, i.v., q 24 h) were half-life of 1.47 and 1.61 hours, volume of distribution of 0.17 and 0.17 L/kg, and systemic clearance of 1.27 and 1.2 ml/kg/min, respectively. Mean serum creatinine concentration was 1.74 and 1.71 for the high and low dosages, respectively, and serum creatinine concentration was not correlated with gentamicin clearance. CONCLUSIONS AND CLINICAL RELEVANCE: Gentamicin administration at a dosage of 4 mg/kg, i.v., every 24 hours, will result in plasma concentrations that are adequate against susceptible bacteria with a minimum inhibitory concentration (MIC) of < or = 2.0 micrograms/ml. Gentamicin administration at a calculated dosage of 6.8 mg/kg, i.v., every 24 hours will result in optimum plasma concentrations against susceptible bacteria with a MIC of < or = 4.0 micrograms/ml.     

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.     

Pharmacokinetics of gentamicin in channel catfish (Ictalurus punctatus)

The pharmacokinetics of gentamicin were determined in male and female Ictalurus punctatus weighing between 0.3 kg and 1.7 kg. Plasma gentamicin concentrations were measured by radioimmunoassay technique. In the 1st experiment, an intracardiac bolus dosage of gentamicin (1 mg/kg) was given to 10 channel catfish. Samples of blood were obtained (by cardiac puncture) immediately before gentamicin was given and at various times over a 24-hour period. The gentamicin half-life was 770 minutes (beta = 0.0009 +/- 0.0003 minute-1). The maintenance therapeutic IV dosage of gentamicin was calculated to be 1.6 mg/kg given at 33.2-hour intervals. In the 2nd experiment, an IM dosage of the drug (1 mg/kg) was given to 9 channel catfish, and samples of blood were obtained at various times over a 24-hour period. The gentamicin half-life was 770 minutes (beta = 0.0009 +/- 0.0002 minutes-1). The maintenance therapeutic IM dosage of gentamicin was calculated to be 3.5 mg/kg given at 33.2-hour intervals. The IM bioavailability of gentamicin in channel catfish was estimated to be 60%. Other pharmacokinetic values were also determined. It was concluded that the therapeutic regimen of choice for gentamicin in channel catfish was 3.5 mg/kg given IM with 33-hour intervals between doses.     

Pharmacokinetics of gentamicin in laboratory rabbits

The pharmacokinetics of gentamicin was studied in 5 healthy adult laboratory rabbits of both sexes. Gentamicin sulfate (5% aqueous solution) was administered rapidly (IV) at a dosage of 3 mg/kg of body weight. Venous blood samples were taken at 0 (baseline), 5, 10, 15, and 30 minutes, and 1, 1.5, 2, 2.5, 3, 4, 5, and 6 hours after gentamicin administration. Serum gentamicin concentration was measured by radioimmunoassay. With the aid of a nonlinear least-squares program, the gentamicin concentration data were found to be best described by a 2-compartment model, with r2 = 0.989. Half-life, as determined from the terminal phase, was 56.6 +/- 2.4 (mean +/- SD) minutes. Calculation of total body clearance provided a mean of 1.69 +/- 0.07 ml/min/kg of body weight. Volume of distribution, calculated from the area under the curve for each animal, was 0.138 +/- 0.005 L/kg.     

Pharmacokinetics and tissue residues of gentamicin in lactating cows after multiple intramuscular doses are administered

Gentamicin was administered IM to 6 healthy, mature, lactating cows at a dosage of 3.5 or 5 mg/kg of body weight every 8 hours for 10 consecutive days (total, 30 doses). Endometrial biopsies were done at 72, 136 or 144, and 216 hours after the first dose was administered. On the 10th day, just before the last dose of gentamicin was administered, blood samples (designated 10th-day base-line samples) were obtained, and serial blood samples were obtained for 144 hours after the last injection was given. The cows were catheterized on the 10th day, and urine was obtained for 10 to 18 consecutive hours. Milk samples were also obtained. The cows were slaughtered at different times after the last dose was given, and samples were taken from 22 tissues and organs. Serum, milk, urine, and tissue gentamicin concentrations were determined by radioimmunoassay. Serum gentamicin concentrations were best fitted to a 2-compartment open model. The mean half-lives for absorption, distribution, and elimination were 0.16 +/- 0.14, 2.59 +/- 0.53, and 44.91 +/- 9.38 hours, respectively. Total body clearance and renal clearance were 1.65 +/- 0.69 and 1.32 +/- 0.25 ml/min/kg, respectively. The percentage of the dose excreted unchanged in the urine at 8 hours after the last dose was given was 98 +/- 15. As expected, of the tissues examined, the gentamicin concentrations in the kidney cortex and medulla were 1,500 times greater than those in serum. Renal function remained within the baseline range during the 10 days of gentamicin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of dose and duration of therapy on gentamicin tissue residues in sheep

The effects of different doses and dosage regimens on gentamicin pharmacokinetics and tissue residues were determined. Five groups of 12 sheep each were given gentamicin IM: group I, 2 mg of gentamicin sulfate/kg once; group II, 6 mg/kg once; group III, 18 mg/kg once; group IV, 6 mg/kg every 24 hours for 3 doses; and group V, 2 mg/kg every 8 hours for 9 doses. Serum concentrations were determined serially until sheep were killed and necropsied. Three sheep from each group were killed at 1, 4, 8, and 12 days after the last dose was administered. Renal cortex, renal medulla, liver, spleen, lung, skeletal muscle, and skeletal muscle at the injection site were assayed for gentamicin. An exponential equation was fitted to the serum concentrations, and various pharmacokinetic variables were determined. Serum clearance tended to increase as the single dose increased (P = 0.0588). Steady-state volume of distribution increased as the single dose was increased (P less than 0.05). Renal cortex contained the highest concentration of gentamicin which decreased in a biexponential manner. Concentrations in all tissues, except the injection site, were dependent upon the amount of the total dose, not the size of the injected dose (P less than 0.05). Concentrations at the injection site were up to 29 micrograms/g of tissue at 1 day after the last dose was given and were dependent upon the amount of total dose from multiple injections, not on the amount of each injected dose (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of repeated administration of tirilazad mesylate on healthy and endotoxemic calves: a pilot study.

Tirilazad mesylate (TM:U74006F), a nonglucocorticoid 21-aminosteroid (lazaroid), is beneficial in the treatment of experimentally-induced ischemic injury following brain and spinal cord trauma, subarachnoid hemorrhage, hypovolemic shock and endotoxemia. This study investigated the effects of TM following repeated administration in sixteen healthy and endotoxemic calves. Group A calves received TM 3 mg/kg IV; group B calves received Escherichia coli endotoxin in increasing doses (0.1 to 20 micrograms/kg IV); group C calves received TM and endotoxin and group D calves received sterile saline (10 mL). Endotoxin, TM and saline were given every eight hours for five days. Mild, transient tachypnea was observed following TM administration. The drug suppressed clinical signs of endotoxemia until larger doses of endotoxin were given. At necropsy no substantial lesions were observed in groups A and D. Groups B and C had lesions consistent with endotoxemia but only group C calves had evidence of abomasal and ruminal ulceration. Although TM may be of benefit in the treatment of endotoxemia, further studies are needed to determine the optimal dosage and potential side effects in the endotoxic bovine neonate.     

Kinetic study of serum gentamicin concentrations in baboons after single-dose administration

This study establishes preliminary pharmacokinetic data on the use of gentamicin sulfate administered IM to baboons. Serum concentrations greater than or equal to 12 micrograms/ml are generally agreed to cause toxicosis in human beings. On the basis of preliminary test results suggesting that the manufacturer's recommended dosage for dogs of 4.4 mg/kg of body weight caused potentially toxic serum concentrations, a dosage of 3 mg/kg was chosen to conduct a single-dose kinetic study in 6 baboons. Using a single-compartment model, the gentamicin serum half-life for IM administration of 3 mg of gentamicin/kg was 1.58 hours, and serum concentrations remained below the potentially toxic concentrations reported for human beings. We suggest that a dosage of 3 mg/kg is safer than a dosage of 4.4 mg/kg administered IM to baboons. Minimal inhibitory concentrations for 2 Pseudomonas aeruginosa isolates were less than or equal to 1 micrograms/ml. On the basis of our measured elimination half-life of 1.58 hours, it is reasonable to suppose that dosing q24 h will be inadequate to maintain therapeutic serum concentrations. We calculate that serum concentrations will remain at or above our measured minimal inhibitory concentration for P aeruginosa (1 micrograms/ml) for 100% of the treatment time if the animal is dosed q 6h, 78% for dosing q 8h, and 52% for dosing q 12h. Therefore, we suggest 3 mg/kg, q 8h or q 6h as appropriate dosing schedules for the use of gentamicin sulfate administered IM to baboons.     

Combined pharmacokinetics of gentamicin in pony mares after a single intravenous and intramuscular administration

Healthy mature pony mares (n = 6) were given a single dose of gentamicin (5 mg/kg of body weight) IV or IM 8 days apart. Venous blood samples were collected at 0, 5, 10, 20, 30, and 45 minutes and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, 30, 36, 40, and 48 hours after IV injection of gentamicin, and at 10, 20, 30, and 45 minutes and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, and 30 hours after IM injection of gentamicin. Gentamicin serum concentration was determined by a liquid-phase radioimmunoassay. The combined data of IV and IM treatments were analyzed by a nonlinear least-square regression analysis program. The kinetic data were best fitted by a 2-compartment open model, as indicated by residual trends and improvements in the correlation of determination. The distribution phase half-life was 0.12 +/- 0.02 hour and postdistribution phase half-life was 1.82 +/- 0.22 hour. The volume of the central compartment was 115.8 +/- 6.0 ml/kg, volume of distribution at steady state was 188 +/- 9.9 ml/kg, and the total body clearance was 1.27 +/- 0.18 ml/min/kg. Intramuscular absorption was rapid with a half-life for absorption of 0.64 +/- 0.14 hour. The extent of absorption was 0.87 +/- 0.14. Kinetic calculations predicted that IM injections of 5 mg of gentamicin/kg every 8 hours would provide average steady-state serum concentrations of 7.0 micrograms/ml, with maximum and minimum steady-state concentrations of 16.8 and 1.1 micrograms/ml, respectively.     

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.     

Phenolsulfonphthalein pharmacokinetics and renal morphologic changes in adult pony mares with gentamicin-induced nephrotoxicosis

Changes in renal function, determined by pharmacokinetics of phenolsulfonphthalein (PSP), and renal morphologic features were examined in adult pony mares given 20 mg of gentamicin sulfate/kg of body weight, IV, q 8 h (group A) n = 7 or isotonic saline solution, IV, q 8 h, n = 5 (group B) for 14 days. Susceptibility of ponies to gentamicin-induced nephrotoxicosis was varied. Two group-A ponies developed acute renal failure and were euthanatized before treatment day 14, whereas 5 group-A A ponies did not develop physical or behavioral abnormalities after 14 days of gentamicin administration. All group-A ponies but none of group-B ponies developed ultrastructural abnormalities of the proximal tubular epithelium, consistent with gentamicin-induced nephrotoxicosis. Significant (P less than 0.05) differences were not detected in pharmacokinetic values of either group. Clearance of PSP was reduced in 4 group-A ponies that developed the most severe gentamicin-induced nephrotoxicosis. Changes in clearance of PSP were significantly (P less than 0.05) correlated with changes in the serum creatinine concentration.     

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)     

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.