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1.
Benzylpenicillin kinetics were investigated in a breed of sheep adapted to life in barren areas. Important pharmacokinetic differences, dependent on reproductive status (control, pregnancy, lactation), were demonstrated. In control ewes, the steady state volume of distribution was 0.23 +/- 0.15 litre kg-1 and the plasma clearance was 12.4 +/- 3.19 ml kg-1 min-1. During pregnancy, these two parameters were not significantly modified. During lactation, the plasma clearance and volume of distribution were significantly higher than during the control period and pregnancy (27.4 +/- 3.22 ml kg-1 min-1 and 0.696 +/- 0.20 litre kg-1, respectively (P less than 0.01). In contrast the mean residence time (25.0 +/- 4.6 minutes) was similar to those of the control period (17.54 +/- 6.25 minutes) and pregnancy (23.18 +/- 5.94 minutes). These modifications in benzylpenicillin kinetics were explained in terms of fluid balance adjustments and renal function adaptation observed during pregnancy and lactation, and it is suggested that an appropriate dosage regimen for benzylpenicillin should take into account the physiological status of the animal.  相似文献   

2.
Plasma disappearance of creatinine as a renal function test in the dog   总被引：2，自引：0，他引：2  
The serum concentration of creatinine at 120 minutes (SC120) after intravenous injection of 88 mg kg-1 of creatinine, the plasma half-life (t1/2) and the plasma clearance of creatinine (PCC) were evaluated as renal function tests in 30 healthy adult dogs and six adult dogs with known or suspected renal disease. The mean SC120 in the normal dog was 0.31 +/- 0.08 mmol litre-1 and in the clinical cases 0.71 +/- 0.19 mmol litre-1. The correlation coefficients between SC120 and renal creatinine clearance (RCC) for the normal dogs and the clinical cases were -0.76 and -0.69, respectively. At 120 minutes after injection, 95 per cent of normal dogs would be predicted to have a serum creatinine concentration below 0.46 mmol litre-1. The mean plasma t1/2 of creatinine for the normal dogs was 107.7 +/- 17.96 minutes, while the clinical cases had a wide range of values (148.8 to 620.1 minutes). Plasma t1/2 of creatinine was correlated with RCC for both the normal dogs and the clinical cases (r = -0.55, r = -0.91, respectively). The mean PCC for the normal dogs was 7.42 +/- 2.22 ml min-1 kg-1 (range 4.95 to 13.28 ml min-1 kg-1). There was a good correlation between RCC and PCC (r = 0.7). The PCC for the clinical cases ranged from 0.76 to 3.37 ml min-1 kg-1. The correlation between RCC and PCC was significant (r = 0.91). Thus SC120, t1/2 and PCC may be useful methods of assessing renal function in dogs with renal impairment insufficient to cause azotaemia.  相似文献   

3.
The oral and intravenous disposition of the anti-thyroid drug propylthiouracil (PTU) was determined in six clinically healthy cats and four cats with naturally occurring hyperthyroidism. Compared with the normal cats, the mean plasma elimination half-life of PTU was significantly (P less than 0.001) shorter in the hyperthyroid cats (77.5 +/- 5.8 minutes compared with 125.5 +/- 3.7 minutes) and the total body clearance of PTU was significantly (P less than 0.05) more rapid in the cats with hyperthyroidism (5.1 +/- 0.8 ml kg-1 min-1 compared with 2.7 +/- 0.2 ml kg-1 min-1). Following oral administration, both the bioavailability (59.7 +/- 4.9 per cent compared with 73.3 +/- 3.7 per cent) and peak plasma concentrations (14.5 +/- 1.6 micrograms ml-1 compared with 18.9 +/- 0.9 micrograms ml-1) of PTU were significantly (P less than 0.05) lower in the hyperthyroid cats than in the control cats. No difference was noted, however, between the apparent volume of distribution for PTU in the two groups of cats. Overall, results of this study indicate that the oral bioavailability of PTU is decreased and PTU disposition is accelerated in cats with hyperthyroidism.  相似文献   

4.
Experiments were conducted with the sheep of Merino breed given water only at a rate corresponding to 0.5% of their live weight for three days. The animals were given feed ad libitum and during the control measurements water was also available to them ad lib. The fourth day the sheep were given no water and no feed and their renal functions were measured by the standard clearance technique. In the water-depleted sheep the diuresis was naturally reduced and the glomerular filtration rate (GFR) was also observed to have decreased from 77.6 +/- 5.3 to 62.2 +/- 4.2 ml X min-1, P less than 0.05. A small, though significant, decrease was also recorded in plasma urea concentration as a result of the reduced intake of food. The amount of excreted urea decreased by 41% (from 354.0 +/- 41.6 to 208.5 +/- 25.5 mumol X min-1, P less than 0.01) without significant changes in fractional excretion and tubular reabsorption of urea. After three days of water depletion the sheep exhibited a tendency of slight natriuresis whereas the excretion of potassium was reduced. Water depletion was also accompanied by a significant increase in the osmolality of plasma (from 298.0 +/- 1.3 to 317.0 +/- 1.8 mosmol X kg-1 H2O, P less than 0.001) and urine from 789.0 +/- 95.0 to 1547.0 +/- 53.0 mosmol X kg-1 H2O, P less than 0.001), without changes in the clearance of free water. On the other hand, the osmotic clearance was reduced as a result of suppressed excretion of urea and potassium (from 2.33 +/- 0.21 to 1.61 +/- 0.17 ml X min-1, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

5.
Fasting is associated with unconjugated hyperbilirubinemia in several species, including the horse. Studies in ponies showed that a 3-day fast decreased plasma clearance of bilirubin, cholic acid, and sulfobromophthalein (BSP). Since these organic anions are conjugated with different substrates, it is possible that observed differences in plasma clearance result from a general decrease in hepatic conjugating capacity during the animals' fasting. To test this hypothesis, the effects of a 3-day fast on plasma clearance of IV injected BSP (4.4 to 5.1 mg/kg), which is conjugated to glutathione, and indocyanine green (ICG; 0.8 to 1.1 mg/kg), which is not conjugated, were studied in 10 healthy horses and 2 ponies with diverted enterohepatic circulations (indwelling T tubes). Blood samples were obtained for 30 minutes after injection, and bile samples from ponies were obtained for 3 hours. Fasting increased plasma bilirubin concentration in all animals studied (from 1.03 +/- 0.337 mg/dl in control animals to 3.49 +/- 1.01 mg/dl in fasted animals). Kinetic values of ICG disappearance were determined from single exponential functions, and those for BSP were determined from both single and curvilinear (2-exponential) functions. Plasma clearance of BSP in fed horses (8.65 +/- 1.02 ml X min-1 X kg-1) was greater than clearance of ICG (3.54 +/- 0.67 ml X min-1 X kg-1), results similar to those reported in dogs, cats, rats, and persons. Fasting significantly decreased fractional plasma disappearance rate of both BSP (-36%) and ICG (-58%) and similarly reduced plasma clearance (BSP,-48%; ICG,-55%).(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

6.
Cefoperazone pharmacokinetics were studied in unweaned calves. The antibiotic was administered to 10 calves intravenously, to eight calves intramuscularly at 20 mg kg-1 and to 10 calves intramuscularly at 20 mg kg-1 together with probenecid at 40 mg kg-1. Serum concentration versus time data were analysed by non-compartmental methods based on the statistical moment theory. The intravenous data were also fitted by a linear, open two-compartment model. The terminal halflife of cefoperazone was 127.9 +/- 28.2 min (mean +/- SD) after intravenous and 136.9 +/- 19.6 min after intramuscular administration. The t1/2 was increased to 257.3 +/- 127.3 min by the co-administration of probenecid. The total body clearance was 8.16 +/- 1.60 ml min-1 kg-1 and the volume of distribution at steady state was 0.713 +/- 0.167 litre kg-1. The mean residence time values were 87.2 +/- 10.6 min after intravenous and 140.3 +/- 20.6 min after intramuscular injection and were increased to 264.5 +/- 99.8 min by the co-administration of probenecid. The estimated mean absorption time was 53.1 min and the estimated bioavailability after intramuscular administration was 76.3 per cent. The minimal inhibitory concentration (MIC90) values of cefoperazone ranged from 0.5 to 2 micrograms ml-1 for Escherichia coli, salmonella groups C, D and E and Pasteurella multocida isolates. Salmonella group B strains appeared to be highly resistant to cefoperazone with MIC90 greater than 32 micrograms ml-1. There were no significant differences between the pharmacokinetic variables calculated by statistical moment theory or compartmental analysis indicating central compartment output of cefoperazone.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

7.
The disposition kinetics and dosage regimen of cephaloridine were investigated in calves following a single intravenous dose of 10 mg.kg-1. The distribution half-life and elimination half-life were 0.16 +/- 0.02 and 1.96 +/- 0.16 h, respectively. The apparent volume of distribution was 0.64 +/- 0.06 l.kg-1 and total body clearance which represents the sum of all clearance processes, was 225.2 +/- 15.1 ml.kg-1.h-1. Based on kinetic parameters, a satisfactory intravenous dosage regimen of cephaloridine in calves would be 11.0 mg.kg-1 repeated every 8 h.  相似文献   

8.
The disposition kinetics and dosage regimen of sulfapyridine were studied in buffalo calves following a single intravenous dose of 100 mg/kg. Distribution half-life (t1/2 alpha) elimination half-life (t1/2 beta) and Vd (area) was 0.181 +/- 0.008 h, 13.4 +/- 0.52 h and 0.59 +/- 0.03 L kg-1, respectively. Total body clearance, which represents the sum of all clearance processes, and tissue/plasma (T/P) ratio were calculated to be 31.1 +/- 2.28 ml kg-1 h-1 and 2.25 +/- 0.09, respectively. A satisfactory intravenous dosage regimen of sulfapyridine in buffalo would be 104 mg/kg followed by 75 mg/kg at 24 h intervals.  相似文献   

9.
Carprofen was administered intravenously to sheep at two dose rates (0.7 and 4.0 mg kg-1), and the pharmacokinetics of the drug studied. Plasma concentrations of the drug were measured by high performance liquid chromatography. Carprofen had a small volume of distribution (Vd[area], 95.5 and 118.4 ml kg-1), a prolonged elimination half-life (t1/2 beta, 26.1 and 33.7 hours) and a slow body clearance rate (Clb, 2.5 ml kg-1 h-1) in sheep.  相似文献   

10.
Pharmacokinetics and renal clearance of ampicillin were investigated in 13 sheep, following one single oral dose of 750 mg. A peak concentration in plasma 0.38 +/- 0.04 microgram/ml (mean +/- SEM) was achieved 95.3 +/- 5.95 min after drug administration. Absorption half-life was 44.4 +/- 4.4 min. The area under the plasma concentration curve was 94.6 +/- 4.5 micrograms.hour.ml-1, while in the case of urine it was 370.5 +/- 28.3 micrograms.hour.ml-1. Biological half-life of ampicillin was 110 +/- 3 min, with an elimination rate constant of 0.0064 +/- 0.0002 min-1. The values for volume of distribution and total body clearance were 8.2 +/- 0.71/kg or 52.0 +/- 4.2 ml/kg/min, respectively. The priming and maintenance doses, using MIC as 0.05 microgram/ml, were suggested to be 8.8 or 8.4 mg/kg, respectively, at an 8-h interval. For MIC of 0.5 microgram/ml, this dose should be 10 times higher. Renal clearance of ampicillin seemed to involve active tubular secretion. Renal excretion indicated either extensive metabolism or excretion through routes other than kidneys.  相似文献   

11.
Pharmacokinetic parameters of thiamphenicol (TAP) were determined after intravenous (i.v.) and intramuscular (i.m.) administration of 30 mg kg-1 of TAP in pigs. Plasma drug concentrations were determined by high performance liquid chromatography (HPLC) Intravenous TAP kinetics were fitted to a bi-exponential equation, with a first rapid disposition phase followed by a slower disposition phase. Elimination half-life was short, at 59.3 (29.4) minutes; volume of distribution at steady state was 0.62 (0.24) 1 kg-1; and plasma clearance was 13.4 (4.5) ml min-1 kg-1. After i.m. administration, the peak plasma concentration (Cmax= 4.1 microg ml-1) was reached in about 60 minutes; these concentrations are lower than those reported in other species. The TAP elimination half-life after i.m. administration, 250.2 (107.1) minutes was longer after than i.v. administration, probably due to the slow rate of absorption from the muscle. The mean bioavailability value for i.m. administration was 76 (12) per cent.  相似文献   

12.
The first pass of a bolus of radioactivity (99mTc) through the heart and lungs was studied in 27 anaesthetised healthy adult mongrel dogs, using a gamma camera with a computer on-line. Bodyweights ranged from 9 to 60 kg, heart rate from 108 to 150 beats min-1. Quantitative analysis revealed that the distribution volume (DV) of the labelled blood, the cardiac output (CO), the stroke volume (SV) and pulmonary blood volume (PBV) were almost proportional to the bodyweight. Specific results were: DV 120 ml kg-1, CO 136 ml kg-1, SV 1.11 ml kg-1, PBV 6.9 ml kg-1. The pulmonary transit time varied between 1.0 and 3.6 seconds. Clinical applicability of the method, including visual inspection of camera images and quantitative analysis of a time-activity curve of the lung, was demonstrated for one dog with an aortic stenosis and another with a left-to-right shunt.  相似文献   

13.
Surgical procedures are described for chronic cannulation of portal vein, ileal vein, abdominal aorta, and carotid artery in pigs. Silastic or Micro-Renathane tubing was used for cannulating portal vein and ileal vein, while carotid artery was cannulated with Micro-Renathane tubing. The lumen of Micro-Renathane tubing was coated with tri-dodecylmethyl ammonium chloride (TDMAC)-heparin complex. The abdominal aorta was cannulated via saphenous artery with vinyl tubing. This allows simultaneous collection of blood samples from hepatic portal vein and systemic artery (carotid or abdominal aorta) and continuous infusion of p-aminohippuric acid (PAH) into ileal vein. The constant PAH infusion provided an indicator-dilution method for estimating the blood flow rate in portal vein. In 13 pigs weighing 54 +/- 2.8 kg, the mean portal vein blood flow rate during the 8-h postprandial period was estimated to be 1,979 ml X min-1 X pig-1 or 37.8 ml X min-1 X kg-1 body weight. By simultaneously measuring the concentration of nutrients and metabolites in the portal and systemic arterial blood and multiplying porto-arterial differences by the estimated portal vein blood flow rate, the net absorption of nutrients (except long-chain fatty acids) and metabolites into hepatic portal system in conscious swine can be quantified.  相似文献   

14.
Experiments were performed with young two-humped camels exposed to 36-hour starvation with free access to water. The renal functions were measured by the standard clearance method. In spite of the administration of 20 micrograms DDAVP, a higher urine flow rate was recorded in the camels subjected to control measurements (feed intake) than in the fasting period (1.45 +/- 0.06 vs. 0.96 +/- 0.06 ml . min-1, P less than less than 0.001). On the second day of fasting the camels had a significantly reduced glomerular filtration rate (GFR 317.5 +/- 23.2 vs. 170.2 +/- 17.4 ml . min-1, P less than 0.001), urea output (700.5 +/- 62.9 vs. 352.2 +/- 64.7 mumol . min-1, P less than 0.005), and fractional excretion of urea (26.9 +/- 2.8 vs. 17.9 +/- 1.7%, P less than 0.01), whereas their tubular resorption. of urea (Reab urea/GFR) increased (6.28 +/- 0.61 vs. 9.12 +/- 0.82 mumol . ml-1, P less than 0.02). No significant difference was found in the concentration of urea in plasma in the fed camels and in fasting camels (8.55 +/- 0.64 vs. 11.18 +/- 1.09 mmol . l-1, N. S.). The creatinine inulin clearance ratio (C creat/Cin) was 0.92 +/- 0.07 when the animals were fed and 1.17 +/- 0.05 when the animals starved (P less than 0.001); this suggests that the clearance of endogenous creatinine is not suitable for GFR measurement in camels under different conditions of nutrition. The kidneys of camels regulate the excretion of urea during short-time fasting mainly through the reduction of glomerular filtration rate and just partly through an increased tubular resorption.  相似文献   

15.
The goals of this study were to determine if the glomerular filtration rate (GFR) in dogs could be estimated by plasma inulin clearance and/or infusion inulin clearance analyses without urine collection, and to compare these results with GFR values obtained by urinary inulin clearance analysis. The dogs included in this study were healthy 20 beagles. Inulin clearance values were obtained by urinary inulin clearance, infusion inulin clearance, and plasma inulin clearance techniques. Urinary inulin clearance was 4.09±0.52 ml min(-1) kg(-1) (body weight); infusion inulin clearance, 4.01±0.49 ml min(-1) kg(-1); and plasma inulin clearance, 4.14±0.66 ml min(-1) kg(-1). The urinary inulin clearance was strongly correlated with infusion inulin clearance and weakly correlated with plasma inulin clearance. The GFR for dogs can be estimated by infusion and plasma inulin clearance analyses by blood sampling alone, without urine collection.  相似文献   

16.
Disposition and local tolerance of a new oxytetracycline (OTC) long-acting formulation were evaluated in camels by measuring the dynamics of creatine kinase. Six camels (Camelus dromedarius) were administered OTC by IV and IM routes according to a 2-period cross-over, study design. Serum OTC concentration was measured, using a microbiological assay procedure. After IV administration (5 mg/kg of body weight), mean residence time was 7.7 +/- 2.8 hours, steady-state volume distribution was 706.1 +/- 168.6 ml.kg-1 and serum clearance was 75.3 +/- 23.2 ml.kg-1.h-1. After IM administration of the long-acting OTC formulation (10 mg/kg), maximal OTC concentration (3.49 +/- 0.44 micrograms.ml-1) was observed after 7.3 +/- 3.5 hours; the mean systemic availability was near 100%, and serum concentration greater than 0.5 micrograms.ml-1 was maintained for about 72 hours. After IM administration, mean control serum activity of creatine kinase was multiplied by a factor of 3.36 +/- 1.55; at 72 hours after OTC administration, the serum creatine kinase activity returned to control values. It was concluded that OTC is an antibiotic of potential interest in camels and that a dosage regimen of 10 mg.kg-1 deserves attention when using a long-acting formulation that has good local tolerance and near total systemic availability.  相似文献   

17.
In 30 clinically healthy dogs (weights 7.5 to 57 kg) and in 41 proteinuric dogs the 131I-hippuran blood disappearance curve after single injection was determined (0 to 90 minutes), described by a bi-exponential function and analysed according to a two compartment model. The dependence of the blood clearance (C), representing an effective renal blood flow, on the bodyweight (W) (kg) could be described with both a linear function (C = 61 + 13.2 W ml min-1) and a power function (C = 30.56 W0.79 ml min-1) in the healthy dogs. The results of the regression between blood clearance and bodyweight were reproducible (r = 0.92, n = 10 residual error 12 per cent, P less than 0.01).  相似文献   

18.
Continuous measurements were performed on 16 untrained boars for VO2, VCO2, and rectal temperature, prior to, during, and after running exercises on an horizontal exercise belt, with speeds set to 1.3 m.s-1 corresponding to something between 23 and 43 kg of body weight b.wt. or 0.7 and 1.3 m.s-1 corresponding to 76 to 86 kg of b.wt. The highest values of VO2 and VCO2 (ml.min-1/kg-1 b.wt.) and of rectal temperature (degrees C) were 36.78 +/- 3.57, 40.23 +/- 6.17, and 41.9 +/- 0.6 in younger animals or 21.49 +/- 2.46, 22.53 +/- 3.12, 40.8 +/- 0.5, 29.3 +/- 5.15, 30.6 +/- 4.77, and 40.7 +/- 0.45 for somewhat older animals for belt speeds of 0.7 and 1.3 m.s-1. Exercise belt speeds of 0.7 to 1.3 m.s-1 were found to be suitable for testing aerobic metabolic capacity of untrained young boars.  相似文献   

19.
The effect of short term starvation on the disposition kinetics of chloramphenicol was determined in goats. The same dosage level (10 mg kg-1) administered intravenously produced higher serum concentrations in the animals when they were starved than when they were not starved. This could be attributed to the significantly smaller (P less than 0.05) volume of the central compartment. Starvation significantly decreased the rate of elimination of chloramphenicol while the apparent volume of distribution of the drug was not altered. A significant decrease in the body clearance, 1.36 +/- 0.95 ml (min kg)-1 in the starved condition compared with 3.78 +/- 2.19 mg (min kg)-1 in the controls, caused a corresponding increase in the half life of chloramphenicol. The decreased rate of elimination was attributed to decreased hepatic microsomal metabolism since starvation did not change the fraction of the dose excreted unchanged in the urine. The clinical significance of the altered disposition of chloramphenicol is that administration at the usual dosing rate would lead to accumulation of the drug and eventual toxicity.  相似文献   

20.
Disposition kinetics and urinary excretion of ceftriaxone were investigated in healthy crossbred calves after its single intravenous administration (10 mg kg-1). Based on kinetic parameters, an appropriate dosage regimen of ceftriaxone in calves was calculated. The peak plasma level of ceftriaxone at 1 min was 84.0 +/- 1.55 micrograms ml-1 which declined to 0.43 +/- 0.05 microgram ml-1 at 8 h. The value of elimination half-life (t1/2 beta), volume of distribution Vd (area) and total body clearance (ClB) were 4.39 +/- 0.63 h, 1.91 +/- 0.19 L kg-1 and 0.31 +/- 0.01 L kg-1 h-1, respectively. Approximately 41 per cent of total administered drug was recovered in the urine within 24 h of its administration. The plasma protein binding of ceftriaxone was found to be concentration dependent with an overall mean of 38.55 per cent. The binding capacity of ceftriaxone to plasma proteins and the dissociation rate constant of protein-drug complex were 20.1 x 10(-8) +/- 18.4 x 10(-8) mole g-1 and 1.07 x 10(-6) +/- 0.52 x 10(-6) mole, respectively. An appropriate intravenous dosage regimen of ceftriaxone in cattle would be 12 mg kg-1 repeated at 24 h.  相似文献   

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