ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1991.tb00801.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Concentration‐time profiles and the rates of absorption, extent of distribution and half‐lives of sulfamethazine (SMZ), administered intravenously, orally as a water solution and as a sustained‐release formulation (CalfSpanrr̀) were determined in 10 healthy sheep. The geometric mean half‐life of elimination of i.v. SMZ was 10.8 h, compared to 14.3 h for the sustained‐release preparation (CalfSpanrr̀) and 4.3 h for the oral water solution. Blood levels of SMZ were at or above 50 ng/ml for more than 48 h for CalfSpanr̀, for 24 h after i.v. SMZ (100 mg/kg body wt), and for less than 24 h after p.o. SMZ (100 mg/kg body wt). The mean bioavailability of the oral SMZ solution was 58.3% (AUCp.oJAUCi.v). The estimated bioavailability of the CalfSpanr̀ preparation was 52.5%. The safety of the sustained‐release preparation was tested by dosing sheep with multiples (one, three and five times) of the recommended dose (one tablet, 8 g SMZ, per 20 kg body wt), once a day for 3 days. Clinical blood chemistries showed a significant increase in serum iron, and a decrease in serum phosphorus in animals treated at the 3x and 5x dose levels. Necropsies of the 5x dose animals did not show any gross signs that could be attributed to SMZ, and histological examination of tissues from the 5x animals revealed no organ pathology. Residues of SMZ in liver, fat, kidney and skeletal muscle were measured in 20 animals that received one bolus per 20 kg body wt. The results indicate that SMZ residues are cleared rapidly, and are at or below the tolerance level of 0.1 mg/kg within 8 days after dosing so that the 18‐day withdrawal time used in cattle would provide an appropriate margin of safety

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1991.tb00802.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

The thiamylal‐and halothane‐sparing effect of diazepam was studied in two experiments using 32 conditioned dogs. Twenty‐four dogs received 0.05, 0.1 or 0.2 ml/kg diazepam or 0.9% saline (placebo) prior to the administration of thiamylal sodium i.v. Eight dogs received 0.1 or 0.2 mg/kg diazepam i.v. or placebo prior to or during halothane anesthesia. All three doses of diazepam significantly decreased the amount of thiamylal required to allow orotracheal intubation. The 0.2 mg/kg i.v. dose of diazepam produced the most significant effects. Premedication of dogs with diazepam did not reduce the concentration of halothane required to maintain anesthesia. The administration of 0.1 and 0.2 mg/kg diazepam i.v. during halothane anesthesia decreased the concentration of halothane required to maintain anesthesia. These studies demonstrate that diazepam reduces the amount of thiamylal required for orotracheal intubation, and when given intra‐operatively reduces the concentratíon of halothane required to maintain an

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1991.tb00803.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Metabolites of the cephapirin ß‐lactam antibiotic have not previously been reported in bovine milk. The principal metabolite was tentatatively identified as desacetylcephapirin by liquid chromatography with UV‐VIS photodiode array (LC/UV‐VIS PDA), and liquid‐chromatography‐mass‐spectrometric (LC‐MS) detection. Synthetic desacetylcephapirin was prepared by incubation of cephapirin in bovine milk and serum at 37d̀C. Also, a method for determining cephapirin in bovine milk and serum was developed. The detection limits for cephapirin and desacetylcephapirin were estimated to be 10 and 50 ug/kg, respectively, for LC/UV‐VIS PDA, and 100 and 50

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1991.tb00804.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

The vascular leakage induced by histamine, bradykinin, serotonin and prostaglandin E1and E2was assessed. The test agents were injected intradermally into the shaved thoracic skin of horses and the vascular leakage estimated either semi‐quantitatively by recording the diameter of the lesions or by measuring the actual volume of extravasated plasma in microlitres using iodine‐125‐labelled human serum albumin (125I‐HSA) as a marker in the blood plasma. Using the latter method, the vascular leakage induced by carrageenin and the effect of coadministered prostaglandins E1and E2upon the vascular leakage of both histamine and bradykinin were also investigated. No obvious lesions resulted when serotonin (10‐2mol/1) was injected but histamine and bradykinin produced circular lesions which increased in diameter for approximately 30 min. The size of the lesions and volume of extravasated plasma was dose dependent. On a molar basis, bradykinin (10‐6mol/1, 10‐5mol/1) was more potent than histamine but they were equipotent at 10‐4mol/1. The size of the lesions induced by carrageenin were independent of their anatomical location on the thorax. Except for the second hour, the hourly volume of vascular leakage increased until the fifth hour when the experiment was concluded. The maximum vascular leakage resulting from the injection of prostaglandin E1or E2(1, 10, 100 or 1000 ng) was 7 μ but when co‐administered with bradykinin (10‐6mol/1), the volume of leaked plasma increased from 29 to 78 μ. No synergy was observed when either prostaglandin was co‐administered wit

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1991.tb00805.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Sodium salicylate was administered to rabbits in order to compare its disposition with that in other major and minor agricultural species. A dose of 44 mg/kg was given orally (p.o.) or intravenously (i.v.), and plasma and urine samples were collected for 36 h and 96 h, respectively. The majority of the drug was excreted as salicylic acid (SA) within 12 h. The major metabolites following an oral dose were salicyluric acid (SUA) and the glucuronide conjugates of SA and SUA. Following i.v. dosing, sulfate conjugates of both SA and SUA were also evident. Both SA and SUA were detected in plasma. Following i.v. administration, SA was distributed with a V55of 0.249 ± 0.082 1/kg and cleared at a rate of 0.0432 ± 0.006 1/h/kg. The biological half‐life, calculated from the terminal disposition rate constant, was 4.3 h (i.v.) or 9.7 h (p.o.). The urinary elimination pattern of SA and metabolites in the rabbit was similar to that previously reported by our laboratories for cattle and goats, although total recovery of the administered dose was not as high as for the latter two species. However, the volume of distribution was larger than for cattle and goats, and rabbits cleared the drug more slowly than those species. As a consequence, the biological half‐life was eight to ten times longer than in the ruminants studied previ

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1991.tb00806.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

The pharmacokinetics and bioavailability of ticarcillin and clavulanate were determined after intravenous (i.v.) or intramuscular (i.m.) administration of ticarcillin disodium (50 mg/kg) combined with clavulanate potassium (1.67 mg/kg) to groups of healthy foals at 3 days and 28 days of age. After i.v. administration of the combination to five foals, the disposition kinetics of ticarcillin and clavulanate were best described using a two‐compartment open model. Mean plasma elimination‐rate constant (ß) and clearance (Clb) for ticarcillin were significantly less (P<0.01), and volume of distribution at steady state (Vd(ss)) was significantly larger (P<0.05), in the foals at 3 days compared with 28 days of age. This indicated that renal excretion mechanisms were immature and ticarcillin was more widely distributed in 3‐day‐old foals. The mean elimination rate constant for clavulanate was significantly less (P<0.01) at 3 days than at 28 days of age. Values of the major kinetic terms describing the disposition of ticarcillin after i.m. administration to five 3‐day‐old foals were not significantly different from values of these parameters in the same foals at 28 days of age. After i.m. administration of the drug combination, plasma clavulanate concentrations peaked significantly later (P<0.01), and the elimination‐rate constant (kd) for clavulanate was significantly less (P<0.01), in 3‐day‐old foals than in 28‐day‐old foals. The bioavailabilities of ticarcillin and clavulanate after i.m. administration in 3‐day‐old foals were 100% and 88.3%, respectively, and in 28‐day‐old foals were 100% and 27.4%, respectively.Mean plasma ticarcillin concentrations exceeded 16 (μg/ml for a longer period after i.m. administration of the drug combination than after i.v. administration to foals of both age groups. By virtue of the frequency of administration required and the painful response elicited by i.m. injection, it is recommended that when the combination of ticarcillin disodium (50 mg/kg) and clavulanate potassium (1.67 mg/kg) is used in foals to treat infections caused by susceptible organisms (MIC ≤16 μ/ml), it should be

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1991.tb00807.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Reduction of the prolonged terminal elimination phase of gentamicin may be caused by diabetes mellitus, irrespective of the model of diabetes. To test this hypothesis, Five normal dogs, three dogs with alloxan‐induced diabetes mellitus, and four dogs with naturally occurring diabetes mellitus (all of which were given exogenous insulin to control hyperglycemia) were given 4.4 mg/kg gentamicin intravenously. Serum pharmacokinetics were analyzed using noncompartmental pharmacokinetics assuming a sum of exponential terms. Gentamicin pharmacokinetics during the first 8 h were the same in normal and diabetic dogs. Over 7 days,MRTin normal dogs (5830 ± 2970 min, mean ± SD) was longer (P<0.01) than in diabetic dogs (136 ± 164 min). In diabetic dogs, Clswas greater (3.01 ± 0.86 ml/min/kg) than in normal dogs (1.45 ± 0.11 ml/min/kg; P<0.01), whereas Vd(ss)was smaller in diabetic dogs (0.405 ± 0.508 1/kg) than in normal dogs (8.56 ± 4.48 1/kg; p,<0.01). Serum gentamicin concentrations were less than 0.020 μg/ml by 2 days in all of the diabetic dogs, but were 0.048 ± 0.018 (μg/ml at 7 days in normal dogs. Thus, diabetes mellitus, either induced by alloxan administration or naturally occurring, abolished the terminal elimination phase of gentamicin disposition in a non‐r

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1991.tb00808.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Six adult domestic shorthair obese cats were given 3‐mg/kg gentamicin sulfate by rapid i.v. and by s.c. injection in a cross‐over design. The plasma concentration time data were analyzed using statistical moment theory with no assumption of a specific compartmental model. Means ± SD for the half‐life, which was calculated from the terminal slope of the log concentration‐time curve, were 1.37 ± 0.24 and 1.24 ± 0.22 h following i.v. and s.c. injection, respectively. The apparent volume of distribution at steady state was 118.55 ± 19.83 ml/kg, and total body clearance was 1.07 ± 0.25 ml/kg/min. Bioavailability was 83.58 ± 14.83% after s.c. administration. The calculated s.c. dose in obese cats to produce an average steady‐state concentration of 4 μg/ml is 2.5 mg/kg every 8 h compared to 3 mg/kg in no

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1991.tb00809.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Pharmacokinetic profiles of the major metabolites of netobimin were investigated in calves after oral administration of the compound (20 mg/kg) as a zwitterion suspension and trisamine salt solution in a two‐way cross‐over design. Blood samples were taken serially over a 72‐h period and plasma was analysed by HPLC for netobimin (NTB) and its metabolites, including albendazole (ABZ), albendazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO2). NTB was occasionally detected in plasma between 0.5 and 1.0 h post‐treatment. ABZ was not detectable at any time. ABZSO was detected from 0.5‐0.75 h up to 32 h post‐administration, with a Cmaxfor the zwitterion suspension of 1.21 ± 0.13 μg/ml andAUCof 18.55 ± 1.45 μg.h/ml, respectively, which were significantly higher (P<0.01) than the Cmax(0.67 ± 0.12 μg/ml) andAUC(8.57 ± 0.91 μg.h/ml) for the trisamine solution. ABZSO2was detected in plasma between 0.75 and 48 h post‐administration. The zwitterion suspension resulted in a Cmax(2.91 ± 0.10 μg/ml) andAUC(51.67 ± 1.95 μg.h/ml) for ABZS02, which were significantly higher (P<0.01) than those obtained for the trisamine solution (Cmax= 1.67 ± 0.11 ug/ml andAUC= 22.77 ± 1.09 ug.h/ml). The ratio ofAUCfor ABZSO2/ABZSO was 2.92 ± 0.26 (zwitterion) and 2.80 ± 0.20 (trisamine). The MRT for ABZSO2was significantly longer (P<0.01) after treatment with the zwitterion suspension than after treatment with the trisamine solution. There was no apparent difference in t1/2 ß, either for ABZSO (from 5.45 to 5.81 h) or ABZSO2(from 5.16 to 5.93 h) between the two formulations. The oral NTB formulations were not bioequivalent, with the zwitterion suspension giving approximately a twofold higher pharmacokinetic profile (AUC)for ABZSO and ABZSO2

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1991.tb00810.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY