Efficacy of ivermectin in injectable and oral paste formulations against eight-week-old Strongylus vulgaris larvae in ponies

A controlled test method was used to evaluate the efficacy of injectable micelle and oral paste formulations of ivermectin (22,23-dihydroavermectin B1) against 8-week-old Strongylus vulgaris larvae in experimentally infected pony foals. The dosage level of the drug in both formulations tested was 0.2 mg/kg. Ponies were euthanatized and necropsied 5 weeks after treatment. Based on the recovery of live vs dead S vulgaris from mesenteric arteries, both formulations were greater than 99% effective. Increased weight gains and marked reductions in the severity of arterial lesions were observed in treated ponies.     

Urine metabolite values in fed and nonfed clinically normal beagles.

Twenty-four-hour excretion of urine metabolites was determined in 33 clinically normal Beagles during periods of consumption of a standard diet and when food was withheld. The goal was to determine normal canine values for urine analytes incriminated in the genesis of calcium oxalate uroliths. During periods when dogs consumed food, dairy urinary excretion of calcium, uric acid, sodium, potassium, magnesium, ammonium, and hydrogen ions were significantly (P = 0.0004, 0.0038, 0.001, 0.0001, 0.0004, 0.0001, and 0.024, respectively) higher than when food was withheld. Urinary excretion of phosphorus, oxalate, and citrate were not significantly different between samples obtained during periods of food consumption and when food was withheld. Male dogs excreted significantly higher quantities of urine oxalate than females during fed (P = 0.003) and nonfed (P = 0.003) conditions. When food was withheld, urinary uric acid excretion was significantly higher in males than females (P = 0.01). Females excreted significantly more urine calcium than males when food was withheld (P = 0.003). Our results indicated that dietary conditions influence the quantity of sodium, potassium, calcium, magnesium, and uric acid excreted in the urine of clinically normal dogs; therefore, dietary conditions should be considered when measuring the concentration of these analytes in urine.     

Pharmacokinetics of cephalexin from two oral formulations in dogs

Six beagle dogs were treated with cephalexin-monohydrate from 2 oral formulations (Rilexine tablets and Cefaseptin dragees, respectively) in a dosage of 25 mg/kg and plasma concentrations of cephalexin were measured over 8 hours. After solid phase extraction of the samples, cephalexin was determined by high pressure liquid chromatography with UV detection. After administration, Cephalexin was absorbed rapidly and mean maximum plasma concentrations of 30.9 and 27.9 micrograms/ml, respectively, were acquired after approximately 1.6 hours. Minimal inhibitory concentrations of < or = 6.25 micrograms/ml for in vitro sensitive bacteria were maintained for about 5 hours. Cephalexin from the tested preparations reached a mean area under the plasma concentration-time curve of 115.3 and 102.4 micrograms.h/ml, respectively. The plasma concentration decreased rapidly with a mean half life period of 1.4 hours in average. The other calculated pharmacokinetic parameters were also in the area of the data for dogs stated in the literature. There was no clear difference in the pharmacokinetics of both products, especially the bioavailability. Furthermore, both formulations were well tolerated clinically.     

Apparent digestibility of crude fibre in ponies fed either a low or high-protein diet

The question addressed was whether apparent crude fibre digestibility in ponies would change after lowering protein intake from adequate to borderline deficient. Four adult ponies were fed a low- and high-protein diet according to a cross-over design. The diets consisted of grass hay and concentrates and provided either 1.5 or 3.6 g digestible crude protein/kg^0.75 per day. The two whole rations provided 2.4 g crude fibre/kg body weight per day. Apparent crude fibre digestibility was not affected by protein intake (low-protein diet: 42.9 ± 4.03%; high-protein diet: 38.1 ± 1.14%, means ± SE, n =4). The low-protein diet caused a significant increase in the ratio of faecal: urinary nitrogen. It is suggested that, when the low-protein diet was fed, sufficient urea flew from the blood into the intestine and ammonia released in the hindgut was conserved so that microbial growth, and thus fibre fermentation, was maintained.     

Bioavailability of magnesium in beef cattle fed magnesium oxide or magnesium hydroxide

Two experiments were conducted to compare Mg bioavailability from Mg oxide (MgO) vs Mg hydroxide (Mg(OH)2) fed in either a completely mixed diet or a mineral supplement. In Exp. 1, these Mg sources were incorporated into completely mixed diets and offered to 15 steers (282 kg) allotted to three treatments: control diet containing .19% Mg, control plus .2% added Mg as MgO, or control plus .2% added Mg as Mg(OH)2. Each calf was fed 5 kg/d of the respective diet during 10-d adjustment and 7-d collection periods. Blood samples were collected on d 1, 3 and 7. Mg supplementation increased (P less than .01) fecal and urinary Mg excretions, whereas apparent Mg absorption (%) and retention were similar (P greater than .10) for all treatments. Plasma Mg concentrations were similar (P less than .10) for calves supplemented with MgO and Mg(OH)2 but were higher (P less than .05) for Mg supplemented than for control calves on d 7. In Exp. 2, these Mg sources were incorporated into mineral supplements and offered free choice to 30 spring-calving beef cows gazing tetany-inducing pastures from March 6 to May 1. Each of three groups of 10 cows was assigned to a 5.7-ha tall fescue pasture and offered either a control supplement or a supplement containing 40% MgO or Mg(OH)2. Blood samplers were collected on d 0, 7, 14, 28, 42 and 56. Plasma Mg concentrations were not different (P greater than .10) for cows offered MgO and Mg(OH)2 but were higher (P less than .01) for Mg-supplemented than for control cows on d 28, 42 and 56.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bioavailability and bioinequivalence of drug formulations in small animals.

Differences in bioavailability of many drugs from their various dosage forms have been shown to be relatively common in human medicine. Although comparable bioavailability ('bioequivalence') is though to ensure comparable clinical effectiveness and safety ('therapeutic equivalence'), the relationship between bioinequivalence and therapeutic inequivalence is less clear. Thus the prevalence of clinically important differences in bioavailability is unknown. While similar concerns have arisen about drug products used in small animal practice, there have been few investigations and some earlier reports are incomplete. However, there are indications of bioinequivalence with enteral formulations of ampicillin, aspirin, chloramphenicol, digoxin, mitotane, oxytetracycline, penicillin V and theophylline. Other studies have suggested bioequivalence with enteral formulations of chloramphenicol, digoxin, phenytoin, oxytetracycline and thyroxine. Limited data for injectable preparations showed bioinequivalence with chloramphenicol and possibly oxytetracycline. There is no reason to expect formulation-related bioinequivalence to be less prevalent in veterinary than in human medicine. Indeed, it may be more common in veterinary practice because other potential influences on bioavailability (food, diseases, other drugs, etc.) are frequently ignored, and cheaper generic products are often favoured for economic reasons.     

Bioavailability of spiramycin and lincomycin after oral administration to fed and fasted pigs

The disposition of spiramycin and lincomycin was measured after intravenous (i.v.) and oral (p.o.) administration to pigs. Twelve healthy pigs (six for each compound) weighing 16–43 kg received a dose of 10 mg/kg intravenously, and 55 mg/kg (spiramycin) or 33 mg/kg (lincomycin) orally in both a fasted and a fed condition in a three-way cross-over design. Spiramycin was detectable in plasma up to 30 h after intravenous and oral administration to both fasted and fed pigs, whereas lincomycin was detected for only 12 h after intravenous administration and up to 15 h after oral administration. The volume of distribution was 5.6 ± 1.5 and 1.1 ± 0.2 L/kg body weight for spiramycin and lincomycin, respectively. For both compounds the bioavailability was strongly dependent on the presence of food in the gastrointestinal tract. For spiramycin the bioavailability was determined to be 60% and 24% in fasted and fed pigs, respectively, whereas the corresponding figures for lincomycin were 73% and 41%. The maximum plasma concentration of spiramycin (C_max) was estimated to be 5 μg/mL in fasted pigs and 1 μg/mL only in fed pigs. It is concluded that an oral dose of 55 mg/kg body weight is not enough to give a therapeutically effective plasma concentration of spiramycin against species of Mycoplasma, Streptoccocus, Staphylococcus and Pasteurella multocida. The maximum plasma concentration of lincomycin was estimated to be 8 μg/mL in fasted pigs and 5 μg/mL in fed pigs, but as the minimum inhibitory concentration for lincomycin against Actinobacillus pleuropneumoniae and P. multocida is higher than 32 μg/mL a therapeutically effective plasma concentration could not be obtained following oral administration of the drug. For Mycoplasma the MIC₉₀ is below 1 μg/mL and a therapeutically effective plasma concentration of lincomycin was thus obtained after oral administration to both fed and fasted pigs.     

Bioavailability and pharmacokinetics of ibuprofen in the broiler chicken

The intravenous, intramuscular and oral pharmacokinetics of ibuprofen in broiler chickens were investigated. In a preliminary study, plasma ibuprofen concentration-time profiles, following i.v. (25 mg/kg) dosing were best described by a 2-compartment model. After intravenous administration, the volume of distribution at steady-state ( V _d(ss)), the total systemic clearance ( Cl _B), the elimination half-life (t_1/2p) and the MRT were 0.303 L/kg, 482.3 ml/h-kg, 2.71 h and 1.02 h, respectively. After intramuscular administration of ibuprofen, the t _max and C _max were 0.37 h, and 42.2μg/mL, respectively, with an estimated bioavailability of 46.7%. After oral administration of ibuprofen, the t _max and C _max were 0.31 h and 23.91 μg/mL, respectively, with an estimated bioavailability of 24.2%. This is a preliminary study, examining the use of ibuprofen in broiler chickens, and should be followed by tissue residue and efficacy studies in different disease states.     

Caecal intussusception in two ponies

One case of caecocaecal intussusception (case 1) and one case of caecocolic intussusception (case 2) in ponies are described. Case 1 showed mild abdominal discomfort for seven days followed by sudden death whereas case 2 showed continuous moderate pain for three weeks. At post mortem examination, case 1 showed intussusception of the base of the caecum into the body whereas in case 2, the entire caecum had invaginated into the right ventral colon. Histopathological examination showed that the lesions in both animals had been present for a long time.     

Bioavailability of oxytetracycline, tetracycline and chlortetracycline after oral administration to fed and fasted pigs

The disposition of oxytetracycline (OTC), tetracycline (TC) and chlortetracycline (CTC) was measured after intravenous and oral administration to pigs. Eighteen healthy pigs (six for each compound) weighing 22-43 kg received a dose of 10 mg/kg intravenously, and 45 mg/kg (OTC and TC) or 40 mg/kg (CTC) orally in both a fasted and a fed condition in a three-way crossover design. The three tetracyclines were present in plasma up to 30 hours after intravenous and after oral administration to fasted as well as fed pigs. The volume of distribution was 1.4, 1.2 and 0.7 L/kg body weight for OTC, TC and CTC respectively. The bioavailability was in general low for all the three tetracyclines. The presence of food did not affect the bioavailability of OTC, which was only 3% in both fasted and fed pigs. For TC there was a significantly higher bioavailability in fasted (18%) than in fed (5%) pigs, whereas for CTC the difference was not significant, being 11% in fasted vs. 6% in fed pigs. Even though the presence of food affected the bioavailability only for TC, it prolonged the absorption phase for all three tetracyclines. Based on the bioavailability and the resulting plasma concentrations, it is concluded that it is not possible to obtain a therapeutically active concentration in plasma or tissues after oral administration of any of the three tetracyclines to fed or fasted pigs.     

Production and clearance of plasma triacylglycerols in ponies fed diets containing either medium-chain triacylglycerols or soya bean oil

The hypothesis was tested that feeding ponies a diet containing medium-chain triacylglcyerols (MCT) instead of soya bean oil causes an increase in the production of plasma triacylglycerols, which, under steady-state conditions, is associated with an increased clearance of triacylglycerols. Six ponies were fed rations containing either MCT or an isoenergetic amount of soya bean oil according to a cross-over design. The concentration of MCT in the total dietary dry matter was about 13%. When the ponies were fed the diets for 3 weeks, plasma triacylglycerol concentrations were 0.42 +/- 0.09 and 0.17 +/- 0.03 mmol/l (mean +/- SE, n = 6; p < 0.05) for the MCT and soya bean-oil treatment, respectively. Plasma triacylglycerol production was assessed using the Triton method and clearance with the use of Intralipid(R) infusion. Plasma triacylglycerol production was 2.91 +/- 0.88 and 0.50 +/- 0.14 micromol/l.min (means +/- SE, n = 4; p < 0.05) for the diets containing MCT and soya bean oil, respectively. It is suggested that the calculated rates of triacylglycerol production are underestimated, the deviation being greatest when the ponies were fed the ration of soya bean oil. Triacylglycerol clearance rates were calculated on the basis of group mean values for both the fractional clearance rate and the baseline levels of plasma triacylglycerols; the values were 4.28 and 3.52 micromol/l.min for MCT and soya bean oil feeding, respectively. The mean, absolute clearance rates as based on those found in individual ponies did not show an increase when the diet with MCT was fed. Nevertheless, it is concluded that the data obtained support our hypothesis.     

Chronic oral therapy with enalapril in normal ponies

Enalapril is an angiotensin converting enzyme (ACE) inhibitor that is frequently used in human, feline and canine patients with cardiac disease. Its use has been associated with impotence in human patients. The purpose of this study was to evaluate if enalapril (0.5 mg/kg PO, q24h) is likely to alter behavior in stallions and to assess its effect on ACE activity at the standard dose used in dogs and cats. Twelve pony stallions were evaluated by physical examination and echocardiography followed by treatment with enalapril (n = 6) or placebo (n = 6) for 2 months. After one month, blood was drawn and stored to evaluate ACE activity in the 2 groups. At the end of the study, repeat physical examination and echocardiography were performed. Physical examination, echocardiographic indices, and reproductive performance were unchanged and there was no suppression of ACE activity. Results of this study suggest that enalapril (0.5 mg/kg PO, q24h) is either poorly absorbed in the horse or is inadequately converted to the active form of the drug, enalaprilat.     

口服不同剂型替米考星在鸡体内相对生物等效性研究

本试验按单剂量口服的方法对健康蛋鸡进行替米考星可溶性粉和替米考星溶液中主要组分替米考星的生物利用度和药代动力学研究。利用HPLC方法分析不同时间点试验鸡血浆中的药物浓度。药物的药动学参数结果显示,替米考星可溶性粉和替米考星溶液的平均血药浓度-时间曲线下面积(AUC0-48)分别为(16.947±0.624)μg/mL.h和(16.020±0.631)μg/mL.h,没有显著差异;二者AUC0-48比值为1.058,Cmax分别为(0.759±0.012)μg/mL和(0.764±0.012)μg/mL,比值为0.993;替米考星可溶性粉和替米考星溶液的t1/2β、C l(s)、t1/2 Ka和V/F(c)均没有显著差异;二者的tmax分别为(1.211±0.036)h和(1.030±0.063)h虽然有显著差异,但并不能以此说明二者生物学的非等效性。试验结果说明,单剂量口服替米考星可溶性粉和替米考星溶液后,替米考星被迅速吸收,消退缓慢,依据生物等效性的重要评判指标,得出替米考星可溶性粉和替米考星溶液在治疗中可以相互替代。     

Evaluation of ivermectin paste in the treatment of ponies for Parascaris equorum infections

Twenty ponies less than 18 months of age and infected with Parascaris equorum were treated with either 0.2 mg of ivermectin/kg of body weight (n = 10) or a placebo (n = 10; controls). Five control and 5 ivermectin-treated ponies were euthanatized 14 and 35 days after treatment, respectively. At necropsy, the small intestinal contents, lungs, and liver were examined for larvae and/or adult P equorum. Significantly (P less than 0.02) higher mean total numbers of P equorum were found in the small intestinal contents of the controls on day 14 (51) and on day 35 (21) than in the ivermectin-treated ponies on days 14 (0) and 35 (3). The efficacy of ivermectin in removing adult and intestinal larvae of P equorum at 14 days after treatment was 100%. The efficacies of ivermectin in removing adults and intestinal larvae of P equorum at 35 days after treatment were 100% and 76.9%, respectively. Gross examination of liver and lung tissues revealed damage as a result of P equorum infections in all ponies. The Baermann technique used on liver and lung tissues did not yield any P equorum larvae. Adverse reactions attributable to treatment were not observed.