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1.
The clearance of inulin and creatinine were almost identical in horses, indicating that creatinine clearance can be used for estimation of the glomerular filtration rate in horses. Trimethoprim (TMP) is excreted in urine by glomerular filtration, active tubular secretion and back-diffusion. The clearance of TMP is highly influenced by urine pH, but also by the plasma concentration of the drug and by the degree of diuresis. The results indicate self-depression of the active tubular secretion of TMP at plasma concentrations above 1–2 μg/ml. The renal excretion of sulphadoxine in horses involves glomerular filtration and a pronounced back-diffusion. The clearance of sulphadoxine is dependent on urine pH and increases with increasing pH. The clearance of N4-acetyl sulphadoxine was higher than the clearance of the parent compound. The renal excretion of N4-acetyl sulphadoxine was shown to involve glomerular filtration, active tubular secretion and back-diffusion.  相似文献   

2.
In experiments on goats it was found that the binding of chlorpromazine (Cpz) to the proteins in plasma and milk ranged between 91–99 and 91–97 %, respectively, and was independent of the drug concentration in the samples. The in vitro binding of chlorpromazine in whole milk (96%) was significantly higher (P<0.01) than the protein binding in skim milk (91%) because the drug was concentrated in the butterfat. The concentration of Cpz was always higher in the milk than in the corresponding plasma samples. The renal clearance of Cpz in goats with normal urine pH was very small (0.16 ml min-1) due to the high degree of plasma protein binding and of back diffusion. The mechanisms involved during the renal excretion of Cpz in goats included glomerular filtration, probably active tubular secretion and pH dependent back diffusion.  相似文献   

3.
The renal and mammary excretion of sulfadimidine was investigated in 8 lactating buffaloes after intravenous administration. The results showed that sulfadimidine was bound to the proteins in plasma (39--59 per cent) and milk (5.5 per cent). The renal handling of sulfadimidine was influenced by the variations in the urinary pH and the concentration of non-protein-bound drug. From the results it is concluded that glomerular filtration, back diffusion and active tubular secretion are involved in the renal handling of sulfadimidine in buffaloes. The results of mammary excretion showed that sulfadimidine is excreted into milk of buffaloes in concentration lower than in plasma. The ratio between the concentration of sulfadimidine in milk and plasma increases when the pH of milk increases. The results are consistant with the theory that drugs are excreted through the mammary gland by passive diffusion.  相似文献   

4.
Raekallio M., M. Hackzell and L. Eriksson: Influence of medetomidine on acid-base balance and urine excretion in goats. Acta vet. scand. 1994,35,283-288.– Seven goats were given medetomidine 5 μg/kg as an iv bolus injection. Venous blood samples were taken repeatedly and urine was collected continuously via a catheter up to 7h after the injection.Medetomidine caused deep clinical sedation. Base excess, pH and PCO2 in venous blood rose after medetomidine administration. There were no significant changes in plasma concentrations of sodium, calcium, magnesium, creatinine or osmolality, whereas potassium and bicarbonate concentrations increased, and phosphate and chloride decreased. Medetomidine increased plasma glucose concentration, and in 4 of 7 goats glucose could also be detected in urine. Medetomidine did not influence urine flow rate, free water clearance, bicarbonate and phosphate excretion or pH, but renal chloride, sodium, potassium, calcium, magnesium and creatinine excretion were reduced.The results suggest that the metabolic alkalosis recorded after medetomidine administration is not caused by increased renal acid excretion.  相似文献   

5.
DAVITIYANANDA, DANIS and FOLKE RASMUSSEN: Mammary and renal excretion of sulphadoxine and trimethoprim in cows. Acta vet. scand. 1974, 15, 340–355. — In 21 experiments on 5 healthy, nonpregnant cows are sulphadoxine and trimethoprim infused intravenously for maintenance of constant levels of the drugs through the experimental periods. The experiments show that both sulphadoxine and trimethoprim are bound to the proteins in blood plasma and milk. Further it is demonstrated that sulphadoxine (an acid) is excreted into milk in concentrations lower than in blood plasma while trimethoprim (a base) is excreted into milk in concentrations higher than in blood plasma. Both results are consistent with the theory that drugs are excreted through the mammary gland by passive diffusion.Glomerular filtration and back-diffusion are both involved in the renal handling of sulphadoxine and trimethoprim. For trimethoprim active tubular secretion is also demonstrated. Both the mammary and renal handling of sulphadoxine as well as trimethoprim are influenced by the pH of milk and urine, respectively. The experiments underline that it is the unionized, non-protein-bound fraction of the drugs which diffuses through biological membranes.sulphadoxine; trimethoprim; mammary excretion; renal excretion; cow.  相似文献   

6.
The renal excretion of N4-acetyl sulphanilamide and N4-acetyl sulphadimidine was studied in 19 experiments with 6 goats during continuous intravenous administration of the 2 sulphonamide derivatives. Deacetylation of both compounds takes place to a small extent only. Further it is shown that both sulphonamide derivatives are bound to plasma proteins to a greater extent than sulphanilamide and sulphadimidine. The excretion of the N4-acetylated sulphonamides is compared with the renal excretion of creatinine. The non-protein-bound fraction of the 2 N4-acetylated sulphonamides is excreted by filtration and active tubular secretion. The renal clearances of the acetyl derivatives are higher than those of the parent compounds.  相似文献   

7.
The effects of plasma protein binding on the elimination of sulphadimethoxine (SDM) were examined after intravenous administration of 6.25, 12.5, 25, 50, 100 and 150 mg/kg to pigs. At an early stage of the experiment, the animals were anaesthetised by inhalation of enflurane to obtain a more exact relationship between plasma concentration and the renal excretion. SDM and its acetylated conjugate, N4-acetylsulphadimethoxine (N4-SDM) were detected in plasma and urine of all animals, and the recovery of the doses was almost complete in two animals with negligible renal excretion of SDM. The percentages of plasma protein binding of SDM and N4-SDM were almost similar, and ranged from 30 to 95%, depending on the plasma concentration. The metabolic clearance of SDM by acetylation increased when the plasma protein binding decreased. These results suggested that the main elimination route of SDM in pigs is acetylation, and that the plasma protein binding can have a large effect on the elimination of SDM in pigs. The effect of plasma protein binding on the renal clearance of SDM was not so evident, because urine pH had a much greater effect on it. The deacetylation of N4-SDM was detected after 25 mg/kg intravenous administration of N4-SDM, which suggests that the metabolic clearance of SDM is part of an acetylation-deacetylation equilibrium. Saturation of the active tubular reabsorption of SDM and of the active tubular secretion of N4-SDM was also suggested after higher doses of SDM.  相似文献   

8.
Pharmacokinetics of sulfamethazine in male, female and castrated male swine   总被引：1，自引：0，他引：1  
The concentration of sulfamethazine in plasma and sulfamethazine and its metabolites in urine were compared in male, female and castrated male swine. A surgical technique for placement of catheters in the urinary bladder was used to facilitate the collection of urine in males and castrated males. The elimination rate of sulfamethazine from plasma and the excretion of parent drug and metabolites into urine did not differ significantly among females, males and castrated male swine.  相似文献   

9.
The pharmacokinetics and the biliary and urinary excretions following intravenous administration of furosemide (5 mg/kg) were investigated in the anesthetized dogs with normal and experimentally reduced renal function. After the administration, furosemide caused diuretic and choleretic response, and was excreted into urine and bile at almost similar rate to plasma concentration decay in normal dogs. Half maximum diuretic response was obtained at 1.5 micrograms/ml of plasma concentration and 100 micrograms/min of urinary excretion rate of furosemide. Acute renal failure was produced in dogs by the intravenous administration of mercuric chloride (HgCl2, 2 mg/kg). In HgCl2-treated dogs, the prolongation of half life (T1/2 beta) and the decrease in plasma clearance were noted with the decreased diuretic response. These changes in parameters appeared to be associated with the decrease in excretion of furosemide into the urine, but not into the bile. Plasma level-diuretic response relationship was extensively shifted to the right in HgCl2-treated dogs, while urinary dose-response relationship did not change significantly between two groups. These results suggest that the decreased response to furosemide in HgCl2-treated dogs seems to be due to the decreased renal clearance rather than to the subsensitivity to furosemide on the site of action.  相似文献   

10.
Cisplatin (90 mg/m2) was administered in a 5-minute bolus IV infusion to dogs at 8 AM (n = 6) or 4 PM (n = 6). Blood and urine samples were collected over a 4-hour period for statistical moment pharmacokinetic analysis. Mean urinary excretion rate of total platinum was increased, whereas mean plasma residence time of ultrafilterable platinum was decreased, in the group treated at 4 PM (PM group), compared with those treated at 8 AM (AM group). Over a 2-week postinfusion-monitoring period, both groups of dogs developed decreases in creatinine clearance, urine/serum osmolality ratio (UOsm/SOsm), specific gravity, and increase in BUN, serum creatinine concentration, urine gamma-glutamyltranspeptidase/urine creatinine ratio (UGGT/UCr), fractional excretion of magnesium, and fractional excretion of phosphate. Urine specific gravity and UOsm/SOsm were significantly decreased, whereas UGGT/UCr and BUN were significantly increased in the AM group, compared with the PM group. The time of administration had a significant effect on the pharmacokinetics of cisplatin, which resulted in significant differences in cisplatin-induced renal toxicosis.  相似文献   

11.
Tilmicosin was injected subcutaneously to lactating ewes once at a dose of 10 mg kg-1 b.wt. to determine its plasma, milk, urine and ruminal juice concentrations. Tilmicosin could be detected in all those fluids 30 minutes after injection. Milk and urine concentrations were higher than those of plasma and ruminal juice. The drug was detectable in milk, urine and plasma for 9, 4 and 3 days after injection, respectively. No amount of tilmicosin could be detected in ruminal juice 12 hours following administration. The mean peak concentration of tilmicosin in plasma and milk (Cmax) were 1.29 and 9.5 micrograms ml-1 and were obtained at (Tmax) 5.235 and 15.093 hours, respectively. The drug was slowly eliminated from plasma and milk as indicated by its long half-life (t1/2el) of 15.4 and 26.2 hours, respectively. The mean binding of tilmicosin to plasma and milk proteins in vitro was 16.8% and 26.8%, respectively. The drug was not bound to ruminal juice at any extent. The rate of tilmicosin renal clearance revealed that it was correspondingly increased with higher blood concentrations. While creatinine clearance showed no significant change after tilmicosin administration. The ratio (fractional clearance) between tilmicosin renal clearance to creatinine clearance was less than one indicating that the glomerular filtration is the main pathway of elimination through kidneys. The rate of ruminal gas fermentation in ewes was inhibited after subcutaneous injection of tilmicosin at a dose of 10 mg kg-1 b.wt. The tested samples taken at different time intervals from the rumen of ewes showed a subsequent reduction in the rate of fermentation as compared to control samples. The reduction was correspondingly increased with the increase of tilmicosin concentration in ruminal juice and returned to normal thereafter.  相似文献   

12.
Pharmacokinetics and urinary excretion of sulphadimidine in sheep and goats   总被引：1，自引：0，他引：1  
Pharmacokinetics and urinary excretion of sulphadimidine were determined in sheep and goats following a single intravenous injection (100 mg/kg). The disposition of the drug was described in terms of exponential expression: C p= Be -βt. Based on total (free and bound) sulphonamide level in plasma, pseudo-distribution equilibrium was rapidly attained and the half-life for elimination was 3.88 ± 0.64 h and 4.00 ± 0.34 h in sheep and goats, respectively. Body clearance, which is the sum of all clearance processes was 88 ± 19 and 55 ± 4 ml/kg/h in sheep and goats. Based on this study a satisfactory intravenous dosage regimen might consist of 100 and 60 mg sulphadimidine/kg body wt for sheep and goats and should be repeated at 12 h intervals. The influence of disease conditions on predicted plasma levels remain to be verified experimentally. Three-quarters of an intravenously injected dose of sulphadimidine was excreted in the urine of sheep and goats within 24 h of administration. The drug was mainly excreted as free amine while acetylated drug constituted 7 and 8% of total drug content in the urine of sheep and goats, respectively.  相似文献   

13.
The pharmacokinetics and urinary excretion of ketoprofen in six healthy mares after the first and last of five daily intravenous doses of 2.2 mg of ketoprofen per kg body weight were investigated using a high-performance liquid chromatographic (HPLC) method for determining plasma and urinary ketoprofen concentrations. Plasma ketoprofen concentrations declined triexponentially after each dose with no significant differences in plasma concentrations or pharmacokinetic parameter values between the first and last doses. The harmonic mean of the terminal elimination half-life of ketoprofen after the first and last dose was 98.2 and 78.0 min, respectively. The median values of the total plasma clearance and the renal clearance after the first dose were 4.81 and 1.93 mL/min/kg, respectively. Total plasma clearance was attributed to renal excretion of ketoprofen and metabolism of ketoprofen to a base-labile conjugate which was also excreted in the urine. Renal clearance of ketoprofen was attributed to renal tubular secretion since renal clearance was greater than filtration clearance. Urinary recovery of ketoprofen during the first 420 min after the first dose accounted for 26.4% of the dose as unconjugated ketoprofen and 29.8% of the dose as a base-labile conjugate of ketoprofen. Total urinary recovery of ketoprofen as unchanged ketoprofen and from base-labile conjugate represented 56.2% of the dose. Plasma protein binding of ketoprofen was extensive; the mean plasma protein binding of ketoprofen was 92.8% (SD 3.0%) at 500 ng/mL and 91.6% (SD 0.60%) at 10.0 μg/mL.  相似文献   

14.
Plasma disposition, protein binding, urinary recovery, and renal clearance of sulfamethazine (SMZ), its N4-acetylsulfamethazine (N4-SMZ), and its 2 hydroxy metabolites--6-hydroxymethylsulfamethazine (SCH2OH) and 5-hydroxysulfamethazine (SOL)--and the glucuronide of the latter were studied in 7 cows and 7 calves to determine the relationship between these values and the age of the animal and dosage applied. A capacity-limited hydroxylation of SMZ into SCH2OH was observed in cows and calves given dosages of 100 to 200 mg/kg. A biphasic SMZ elimination curve and steady state in SCH2OH plasma concentration (6 to 15 micrograms/ml) were observed. The N4-SMZ plasma concentration-time curve was parallel to that of SMZ at the dosages and in all animals. The total body clearance and the cumulative urinary recovery (expressed as percentage of the dose) for SMZ and its metabolites depended on drug dosage and age of the animals. At dosages of SMZ less than 25 mg/kg, the main metabolite in the urine of calves and cows was SCH2OH (23% to 55.2%), whereas in calves given a larger dosage (100 mg/kg), the N4-SMZ and SOH percentages increased. The plasma protein binding of SMZ and its metabolites depended on the SMZ plasma concentration. Hydroxylation lowered the protein binding (from 75-80%) to 50%. The renal clearance of SMZ was dependent on urine flow in all animals. The renal clearance of the SCH2OH metabolite was 2 to 3 times greater than the creatinine clearance value; thus, this compound was excreted by glomerular filtration and partly by tubular secretion.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

15.
Four diets were formulated to contain: 16% protein and 0.4% phosphorus--diet 1; 16% protein and 1.4% phosphorus--diet 2; 32% protein and 0.4% phosphorus--diet 3; and 32% protein and 1.4% phosphorus--diet 4. Forty-eight dogs were fed diet 1 for 3 months after surgical reduction of renal mass, then were allotted to 4 groups of 12 dogs each, with equal mean values for glomerular filtration rate (GFR). Dog of groups 1-4 were fed diets 1-4, respectively, for 24 months. Data collected from the dogs during and at termination of the study were analyzed statistically for effects of dietary protein, phosphorus (P), time, and interactions between these factors. During the 24 months of study, 24 dogs developed uremia and were euthanatized for necropsy. Necropsy also was performed on the remaining 24 dogs after they were euthanatized at the end of the study. Dog survival was significantly enhanced by 0.4% P diets (vs 1.4% P diets), but survival was not significantly influenced by amount of dietary protein. The 0.4% P diets (vs 1.4% P diets) significantly increased the period that GFR remained stable before it decreased, but dietary protein did not have significant effect. Significant blood biochemical changes attributed to P, protein, and time were identified during the study. Terminally, plasma parathyroid hormone concentration was significantly increased from prediet values in all groups of dogs. Urine protein excretion was not significantly affected by dietary amount of either protein or P, when measured by either timed urine collection or urine protein-to-creatinine ratio.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

16.
Glomerular filtration rate (GFR) is estimated by means of clearance, defined as the volume of plasma that has been cleared of a particular substance per unit time. Glomerular filtration rate may be estimated by measuring the renal clearance of a filtration marker using data from both urine and plasma or by plasma clearance using only plasma data. Several alternative pharmacokinetic models are used for the calculation of clearance using various filtration markers with slightly different pharmacokinetic properties. The purpose of this article is to discuss how the choice of marker and pharmnacokinetic model may influence estimated GFR values and to elucidate commonly used methods and reported GFR values in the dog.  相似文献   

17.
Dogs with ligated common bile ducts were used to determine effects of cholestasis on pharmacokinetics of digoxin and digitoxin. Forty-three dogs were assigned to: group 1--sham-operated controls (n = 13); group 2--dogs with ligated common bile duct (n = 17); group 3--dogs given phenobarbital for 2 weeks before common bile duct was ligated (n = 11); or group 4--dogs with an induced biliary fistula (n = 2). Digoxin (group A) or digitoxin (group B) was given as single IV injections, and digitalis concentration in plasma was measured by radioimmunoassay. In 18 dogs given digoxin, differences in plasma digoxin concentrations among groups 1A to 3A were not significant (P greater than 0.1). Plasma elimination rate of digoxin was delayed in group 2A. Group-3A dogs had a shortened beta phase half-life (t1/2 (beta] and a decreased distribution volume. In 25 dogs given digitoxin, group-2B dogs maintained a significantly higher plasma digitoxin concentration (P less than 0.01) and had a significantly longer t1/2 (beta] than did dogs in groups 1B and 3B (P less than 0.05). In group-3B dogs, plasma digitoxin concentration was decreased and t1/2 (beta] of digitoxin was shortened. In 10 group-B dogs given 3H-digitoxin (groups 1B, 2B, and 4B), the excretion of total radioactivity in urine and bile was 15 to 20 and 7% of the dose, respectively in the first 24 hours. Most radioactivity in urine and bile was a dichloromethane-unextractable fraction.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

18.
Plasma clearance of creatinine was evaluated for assessment of glomerular filtration rate (GFR) in dogs. In 6 healthy dogs (Experiment 1), we determined 24-hour urine clearance of endogenous creatinine, plasma, and urine clearances of exogenous creatinine administered at 40, 80, and 160 mg/kg in a crossover design (linearity study), plasma iothalamate clearance, and plasma and urine clearances of 14C-inulin. In Experiment 2, plasma creatinine and iothalamate clearances were compared, and a linearity study was performed as for Experiment 1 in 6 dogs with surgically induced renal impairment. Experiment 3 compared plasma creatinine clearance with plasma iothalamate clearance before and 3 weeks after induction of moderate renal impairment in 6 dogs. Plasma creatinine clearances were calculated by both noncompartmental and compartmental analyses. In Experiment 1, plasma inulin clearance was higher (P < .001) than other clearance values. Plasma creatinine clearances at the 3 dose rates did not differ from urine inulin clearance and each other. In Experiment 2, plasma creatinine clearances were about 14% lower than plasma iothalamate clearance (P < .05). In Experiment 3, decreases in GFR assessed by plasma clearances of iothalamate and creatinine were similar. Renal failure decreased the daily endogenous input rate of creatinine by 25%. Limiting sampling strategies for optimizing GFR calculation were proposed, allowing an error lower than 6.5% with 4 blood samples. These results suggest that determination of plasma creatinine clearance by a noncompartmental approach offers a reliable, inexpensive, rapid, and convenient means of estimating GFR in routine practice.  相似文献   

19.
The disposition of sulfatroxazole (STZ) has been studied in goats and pigs after intravenous administration of a single dose. The percentage of protein-binding decreased with increasing plasma concentration in both species. At 100 micrograms/ml about 85% was bound to plasma proteins in goats, while the corresponding value was only 55% in pigs. Two metabolites of STZ were isolated from urine and identified as N4-acetyl-STZ and 3-sulfanilamido-4-methyl-5-hydroxy-methyl-isoxazole (5'-OH-STZ). The goats excreted about 80% of the dose in urine. The majority (64%) was excreted as unchanged STZ, while N4-acetyl-STZ and 5'-OH-STZ made up 19% and 18%, respectively. The pigs excreted 95% of the dose in urine. Unchanged STZ amounted to 30% and N4-acetyl-STZ to 70% of the urinary excretion in pigs, while there were only traces of 5'-OH-STZ.  相似文献   

20.
The concentrations of magnesium and calcium in the serum and urine and their rates of clearance were determined in cattle with renal tubular dysplasia, an autosomal recessive hereditary disease associated with a deletion of the paracellin-1 gene in Japanese Black cattle. There were no significant differences in the serum or urine magnesium concentrations between normal cattle and cattle which were heterozygous or homozygous for the condition. Serum calcium concentrations tended to be lower in the homozygous cattle, and the serum creatinine and urea nitrogen concentrations were significantly higher in the homozygous cattle. The ratio of magnesium:creatinine and the fractional excretion of magnesium were higher in cattle with the disease than in normal cattle. There were no significant differences in urine calcium concentration, the calcium:creatinine ratio, and fractional excretion of calcium between normal cattle and cattle which were homozygous or heterozygous for the condition. The creatinine clearance was significantly lower in the homozygous cattle than in normal cattle. The clearance, excretion rate, reabsorption rate and reabsorption rate:clearance ratio of magnesium in cattle with renal tubular dysplasia were significantly lower than in normal cattle. The clearance rate and reabsorption rate of calcium were also significantly lower in the affected cattle, but the excretion rate and reabsorption rate:clearance of calcium were not different between the normal cattle and the cattle homozygous for the condition. In cattle with the condition the rate of reabsorption of magnesium by the kidneys was low, but the rate of reabsorption of calcium was normal.  相似文献   

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