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.     

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.     

Oral clindamycin disposition after single and multiple doses in normal cats

Eighteen normal cats were randomly allocated into three treatment groups and dosed with clindamycin aqueous solution for 10 days at a dosage rate of: (1) 5.5 mg/kg b.i.d.; (2) 11 mg/kg b.i.d.; or (3) 22 mg/kg once daily. Serum disposition of clindamycin was determined after the first and last dose of clindamycin was given, and was analyzed using model-independent pharmacokinetics by both the trapezoidal rule method and the predictive equation method. Complete blood counts and clinical chemistries were determined before and after the study. The trapezoidal rule method produced similar mean results with much less variance than the predictive equation method. Mean residence time was longer (P less than 0.05) after the high dose (393 +/- 77 min) than after either the low or medium doses (276 +/- 51 and 274 +/- 45 min, respectively). Oral volume of distribution (Vd(ss)/F) after the high dose (3.06 +/- 0.92 l/kg) was larger (P less than 0.05) than that after the low or medium doses (1.62 +/- 0.30 and 1.76 +/- 0.53 l/kg, respectively). Oral Vd(ss)/F was significantly smaller (P less than 0.001) after the last dose than after the first dose when analyzed by treatment group. Significant (P less than 0.01) decreases in the leukogram and erythrogram were observed, due to the large amount of blood collected for drug analysis. No clinical signs of drug intoxication were observed, and no drug-related necropsy findings were found.     

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)     

The pharmacokinetics and tissue levels of polymyxin B, colistin and gentamicin in calves

Following a single intravenous injection of polymyxin B, colistin (5 mg/kg, each) and gentamicin (3 mg/kg) to calves, the decline in serum antibiotic concentration generally suggested a three-compartment (open system) pharmacokinetic model. Tissue binding is a dominant factor in the distribution and elimination kinetics of the drugs. Less than 65% of the dose of polymyxin B and colistin was recovered in the urine during 48 h after treatment. Concentrations of nonbound polymyxin B and colistin in the kidney, liver, lung, heart, and skeletal muscles were similar to total (free and bound) serum drug levels, but considerably higher concentrations were found, in bound form, in chloroform-ethanol extracts of these organs.
At 24 h after treatment, more than 50% of the doses of polymyxin B and colistin were present bound to the tissues; the largest amount was in the skeletal muscles. Gentamicin was concentrated in the kidney, predominantly in the free form. At 48 h after treatment the amount of gentamicin in the kidney was 6.3% of the administered dose, being more than five times greater than the corresponding amounts of polymyxin B and colistin.
The extent of tissue uptake of polymyxin B and colistin limits the usefulness of kinetic values, which are derived from the analysis of serum drug levels, for the purpose of designing dosage schedules. The strong affinity of the polymyxins to the muscle tissue, and gentamicin to the kidney, can result in drug residues persisting in the body for several weeks.     

Tissue concentrations of clindamycin after multiple oral doses in normal cats

Eighteen normal cats were randomly allocated into two blocks with three treatment groups and dosed orally with clindamycin aqueous solution for 10 days at a dosage rate of 5.5 mg/kg twice daily (Group 1), 11 mg/kg twice daily (Group 2), or 22 mg/kg once daily (Group 3). At the end of dosing, all cats were killed and tissues were taken for clindamycin concentration analysis. Clindamycin was extracted from tissues using solid-phase extraction columns followed by microbiological assay of clindamycin using a cylinder plate assay using M. luteus. Recovery from each tissue was determined by inoculating known concentrations of clindamycin into drug-naive tissues and comparing the observed concentration from the expected concentration. Confirmation that the bioassay detected clindamycin and not N-desmethylclindamycin, its active metabolite, was done using gas-chromatography-mass-spectrometry. Concentrations were highest in the lung, with tissue:serum ratios greater than 3 in all groups. Concentrations were higher in Group 3 than Group 1 (P less than 0.05). Only liver concentrations in Group 3 were statistically higher than in Group 2, although all tissues except bone marrow and CSF had numerically higher concentrations in Group 3 than Group 2. The tissue:serum ratio was greater than 1 in all tissues studied except bone, cerebrospinal fluid, brain, and skeletal muscle.     

Gentamicin dosage in foals aged one month and three months

The absorption and disposition kinetics of gentamicin were compared at two dosage levels (2 and 4 mg/kg bodyweight [bwt]) in one- and three-month-old foals. Following intramuscular (im) injection of single 2 mg/kg bwt doses, the drug was absorbed rapidly and produced peak serum concentration (18.2 mu 5.3 +/- g/ml, n = 8) at 30 mins. Much wider variations were associated with the amount of drug absorbed and the serum gentamicin concentrations after administration at the higher dosage level. The half-life of gentamicin was similar in the one-month-old (3.7 +/- 1.7 h, n = 8) and three-month-old (3.3 +/- 0.8 h, n = 8) foals, and was independent of the dose. One-month-old foals did not appear to have a deficiency in renal excretion of gentamicin. The minimum inhibitory concentration of gentamicin for Corynebacterium equi and certain other equine bacterial isolates was less than 0.195 microgram/ml. It was concluded that 2 mg/kg bwt administered by im injection at 8 to 12 h intervals, depending on the severity of the infection, could be recommended as the dose rate for treatment of systemic infections caused by microorganisms that are susceptible to gentamicin.     

阿维菌素长效注射液(油悬剂)对绵羊痒螨的疗效试验

为了研究阿维菌素长效注射液(油悬剂)对绵羊痒螨疗效,将60只自然感染痒螨绵羊随机分为3组,每组20只。第1组每千克体重颈部皮下注射1 mg的阿维菌素油悬剂,第2组注射0.2 mg的阿维菌素普通注射液,第3组为不给药对照组。在给药后第7、14、21、28、35、42、49、56、63、70天对所有绵羊进行螨虫检查和计数,每天观察病变。结果表明:给自然感染痒螨的绵羊皮下注射1 mg/kg的阿维菌素长效注射液(油悬剂)可在给药后7 d内将痒螨完全杀灭,在给药后63 d内防止绵羊被痒螨再感染,其持效期远长于阿维菌素普通注射液(约为14 d)。     

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).     

Thermopsis montana-induced myopathy in calves

Six heifer calves were administered the dried and ground whole plant of Thermopsis montana by gavage once daily for 2 to 4 days at an initial dosage rate of 1 g/kg of body weight. Two of the 6 heifers died after the second dose, and the remaining 4 calves were humanely killed and their tissues were examined. Serum creatine kinase and aspartate transaminase activities were significantly (P less than 0.05) increased after initiation of plant administration. All calves had skeletal muscular degeneration or evidence of regeneration and repair of damaged myofibers in all skeletal muscle groups examined. Myoglobinuria and cardiac muscle degeneration were not detected in any of the calves.     

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.     

泰地罗新注射液对猪传染性胸膜肺炎的临床疗效试验

将泰地罗新注射液分为高、中、低（8、4、2 mg /kg bw）3个剂量组分别肌肉注射治疗猪传染性胸膜肺炎,同时设默沙东动物保健品有限公司的泰地罗新注射液为对照组,按4mg /kg bw给药,给药一次。结果表明,泰地罗新注射液中（4mg/kg bw）、高（8mg/kg bw）剂量对人工感染传染性胸膜肺炎病猪的有效率和治愈率无显著差异（P＞0.05）,与默沙东动物保健品有限公司生产的泰地罗新注射液推荐剂量（4mg/kg bw）的效果相当。试验结果表明泰地罗新注射液按一次量,每1 kg体重4mg肌注,对猪传染性胸膜肺炎有良好的治疗效果。     

Penicillin concentrations in serum, milk, and urine following intramuscular and subcutaneous administration of increasing doses of procaine penicillin G in lactating dairy cows.

Eight healthy, non-pregnant, crossbred Holstein dairy cows (557-682 kg) within their first 3 months of lactation (13-21.5 kg of milk/day) were used. Cows were kept in tie stalls for the whole experiment. The 8 cows were randomly assigned to 2 (IM and SC) 4 x 4 balanced Latin square design experiments. Doses of procaine penicillin G (PPG) (300000 IU/mL) in each square were 7000, 14000, 21000 and 28000 IU/kg and were injected IM or SC once daily for 5 consecutive days. Volumes of PPG per site of injection never exceeded 20 mL. Blood was collected to determine the Cmax, Tmax, and AUC; urine and milk were also taken to measure the persistence of PPG in these fluids. Results show that serum Cmax and Tmax were only slightly affected by increasing the doses or the route of administration, whereas the AUC was linearly increased in relation to the dose injected in both modes of injection. In the urine, Cmax varied from 160 to 388 IU/mL and Tmax from 72-120 h during 5 consecutive days of PPG injection. A dose effect in Cmax was observed only for the IM route of administration and no variation (P > 0.05) was found between the IM and SC routes. Milk Cmax concentrations were only increased by the dose regimen in the IM group. At doses of 21000 and 28000 IU/kg, the IM group had a higher (P > 0.05) Cmax when compared with the SC groups. Milk PPG residues were not detectable over 96 h following the last IM injection, independently of the dose injected. However milk PPG residues were detected for up to 132 h following the last SC injection. These results show that when PPG is injected IM once daily in volumes not exceeding 20 mL/site at doses as high as 28000 IU/kg, the withdrawal period should be at least 96 h. Therefore, in the present model, there was no advantage to inject PPG by SC route to improve PPG kinetic parameters as the AUC, Cmax, or Tmax.     

The effect of niclofolan on desert sheep experimentally infected with immature Fasciola gigantica

Eight desert sheep were each infected orally with 500 metacercariae of Fasciola gigantica and, after 4 weeks, four of the animals were given niclofolan orally at the recommended therapeutic dose rate of 7 mg/kg, the other four remaining as controls. One week later, the animals were slaughtered and the fasciocidal effect of the drug was evaluated on the basis of worm burden, haemogram, some plasma constituents, and gross and histopathological lesions of the liver, as indicators of efficacy. The treatment was found to be ineffective, the degree of infection remaining the same as in the untreated control group. The experiment was repeated using eight infected sheep: four were given the drug orally at a dose rate of 10.5 mg/kg, i.e., 1.5 times the recommended dose; and the same parameters were measured as described above. The drug failed to cure the infected sheep, and caused depression, anorexia and weakness. In a third experiment six sheep were infected as before and three were treated with niclofolan by deep i.m. injection at the recommended therapeutic dose of 2 mg/kg. A week later the animals were killed and examined as before. The drug was effective in treating the infection and produced no untoward effects except for transient signs of pain at the site of injection. It seems possible that the oral dose, unlike the i.m. dose, of niclofolan is not absorbed and/or metabolized sufficiently to prevent elimination of the infection.     

Xylazine causes transient dose-related hyperglycemia and increased urine volumes in mares

Xylazine given IV at doses of 0.5, 1.0, and 1.5 mg/kg to mares caused a significant (P less than 0.05) dose-related increase in serum glucose concentration and urine volume. Serum glucose concentrations as much as 150 mg/dl were recorded in mares after they were given the largest xylazine dose. The greatest urine volume, similar to changes in peak glucose concentration, always occurred during the first hour after dosing with xylazine and averaged 1.82, 3.93, and 5.68 ml/kg/hour after the 0.5-, 1.0-, and 1.5-mg/kg doses, respectively, were given. Urine osmolality and specific gravity were significantly (P less than 0.05) inversely related to urine volume. Although serum glucose concentrations were significantly increased above those measured after IV injection of saline solution, significant glucosuria was not detected.     

The toxicity of phomopsin for sheep

Pure phomopsin was administered to young Merino x Border Leicester wethers by single subcutaneous (SC) and by single and multiple intraruminal (IR) injection. The toxicity after IR injection was influenced by the size of individual doses and the time over which the total dose was given. At high levels of ingestion the toxicity of phomopsin may be limited by absorption rates; with low daily doses the capacity to repair liver damage may be sufficient to prevent cumulative effects. By SC injection a single dose of 10 micrograms/kg approximated the LD50. By IR injection the overall clinical, biochemical and histological responses closest to these of this SC dose resulted from a single dose of 1,000 micrograms/kg. The same total dose administered at daily rates of 50 or 200 micrograms/kg was more toxic and killed all sheep. A single dose of 500 micrograms/kg caused significant liver damage, but no deaths. Single doses of 125 and 250 micrograms/kg and repeated daily doses of 12.5 micrograms/kg over 16 weeks caused no detectable tissue damage. Inappetence was the most sensitive indicator of phomopsin toxicity. About 10% of the sheep differed substantially from the rest of the flock in their susceptibility to phomopsin poisoning.     

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.     

Effects of naloxone on ad libitum intake and plasma insulin, glucose, and free fatty acids in maintenance-fed sheep

The dose-dependent effects of naloxone on feed intake, and plasma chemicals (insulin, glucose, FFA) purportedly involved in feed intake regulation, were determined in 16-hr fasted sheep that were lean and chronically fed maintenance. Dorset ewes (n = 5) were treated with 0 (saline), 0.3, 1 or 3 mg/kg of naloxone in a generalized randomized block experiment with at least 7 d between successive doses. Feed intakes and plasma insulin, glucose and FFA were determined frequently during 24 hr of ad libitum intake after each naloxone treatment. The 0.3, 1 and 3 mg/kg doses of naloxone reduced (P less than 0.01) the 4-hr feed intake by 30, 40, and 60% respectively, whereas the initial feed intake (10 min) was decreased (P less than 0.05) 45% only by 3 mg/kg naloxone. However, total 24-hr intakes were similar across all doses because intakes between 4 and 24 hr of feeding in sheep treated with 0.3 (839 g), 1.0 (802 g) and 3.0 (1330 g) mg/kg naloxone exceeded (P less than 0.01) that in saline-treated sheep (391 g). Feeding-induced changes in plasma insulin, glucose and FFA concentrations were independent of naloxone treatment, suggesting that endorphinergic control of feed intake may not involve coincidental changes in plasma insulin, glucose and FFA levels which are thought to play a role in systemic regulation of appetite in animals. The endorphinergic regulation of appetite in sheep may involve the central nervous system, rather than peripheral opiate mechanisms that utilize blood-borne signals. Further, the ability of naloxone to suppress appetite in sheep appears inversely related to the duration of fasting or severity of negative energy balance.     

Pharmacokinetics of potassium bromide in adult horses

OBJECTIVE: To determine the pharmacokinetics of potassium bromide (KBr) in horses after single and multiple oral doses. ANIMALS: Twelve adult Standardbred and Thoroughbred mares. PROCEDURE: Horses were randomly assigned to two treatment groups. Group 1 horses were given a single oral dose of 120 mg/kg potassium bromide. Part 2 of the study evaluated a loading dose of 120 mg/kg KBr daily by stomach tube for 5 days, followed by 40 mg/kg daily in feed for 7 days. Serum concentrations of KBr were measured to construct concentration versus time curves and to calculate pharmacokinetic parameters. Treated horses were monitored twice daily by clinical examination. Serum concentrations of sodium, potassium and chloride ions and partial pressures of venous blood gases were determined. RESULTS: Maximum mean serum concentration following a single dose of KBr (120 mg/kg) was 423 +/- 22 microg/mL and the mean elimination half-life was 75 +/- 14 h. Repeated administration of a loading dose of KBr (120 mg/kg once daily for 5 d) gave a maximum serum concentration 1639 +/- 156 microg/mL. The administration of lower, maintenance doses (40 mg/kg once daily) was associated with decreased serum bromide concentrations, which plateaued at approximately 1000 microg/mL. Administration of KBr was associated with significant but transient changes in serum potassium and sodium concentrations, and possible changes in base excess and plasma bicarbonate concentrations. High serum concentrations of bromide were associated with an apparent increase in serum chloride concentrations, when measured on an ion specific electrode. CONCLUSIONS: and clinical relevance Loading doses of 120 mg/kg daily over 5 d and maintenance doses of approximately 90 mg/kg of KBr administered once daily resulted in serum bromide concentrations consistent with therapeutic efficacy for the management of seizures in other species. The clinical efficacy of this agent as an anticonvulsant medication and/or calmative in horses warrants further investigation.     

Effect of silymarin and vitamin E on gentamicin-induced nephrotoxicity in dogs

Drug-induced nephrotoxicity is an important cause of renal failure in dogs. Aminoglycoside antibiotics, such as gentamicin, can produce nephrotoxicity in dogs, due to in part to an imbalance of pro- and antioxidants (oxidative stress). Silymarin (the mixture of flavonolignans extracted from Silybum marianum) has potentially beneficial antioxidant properties. A control group (saline, group 1, n = 5) was compared with dogs that were administrated gentamicin by intramuscular injection, at dosage of 20 mg/kg, once daily for 9 days (groups 2-5, n = 5 per group). The effects of vitamin E (group 3) and silymarin (group 4) alone and in combination (group 5) were compared for induced nephrotoxicity. Renal function was assessed using serum biochemical markers (creatinine and urea). Malondialdehyde (MDA) concentration were measured as a marker of lipid peroxidation. The activity of total serum antioxidants (TSAO) was assessed as a marker of antioxidant defences. Serum creatinine and urea concentrations were increased significantly and TSAO was decreased significantly in group 2 compared with group 1. Serum creatinine concentrations but not urea concentrations were significantly lower in groups 3 and 4 than in group 2 (P = 0.001). Serum MDA concentrations was significantly different between groups 2 and 3 (P = 0.01), 2 and 4 (P < 0.001) and 4 and 5 (P = 0.01). TSAO activity was significantly in group 4 (silymarin) than in group 2 (P = 0.002). Silymarin and vitamin E decreased gentamicin-induced nephrotoxicity in dogs.