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1.
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   

2.
The effects of furosemide (0.55 mg/kg IV) on the plasma and urinary fentanyl (PFE UFE) concentrations were studied during steady-state conditions. The PFE during the steady-state period was 0.31 +/- 0.027 ng/ml, with no significant changes occurring, even though the rate of excretion of fentanyl (EX) increased during the 1st hour from 112.0 +/- 21.6 to 534.5 +/- 82.9 ng/minute. The EX returned to control levels within 3 hours, as did the UFE. The injection of furosemide increased glomerular filtration rate from 1.97 +/- 0.21 to 3.81 +/- 0.75 ml/kg/min. The fractional reabsorption decreased from a control of 70.3 +/- 6.2% to 25.2 +/- 2.3% during the 1st hour, returning to control levels at 3 hours after furosemide was given. The total body clearance of fentanyl increased slightly during the peak period of diuresis. The return of EX, fractional reabsorption, UFE, and clearance of endogenous creatinine to control levels occurred before the return of urine specific gravity, indicating the ability of the kidney to concentrate fentanyl before its water concentrating capacity had returned.  相似文献   

3.
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   

4.
The pharmacokinetic disposition of theophylline was determined by high-performance liquid chromatographic analysis of plasma samples from six healthy, adult horses following the administration of intravenous aminophylline (dosed at 9.94 mg/kg as theophylline), immediate-release aminophylline tablets (dosed at 9.94 mg/kg as theophylline), and sustained-release theophylline tablets (dosed at 20 mg/kg). The elimination rate constant (lambda z), apparent volume of distribution (Vz), and clearance (Cl) determined by compartmental analysis of the intravenous data were 0.07 +/- 0.01 h-1, 0.80 +/- 0.06 l/kg, and 0.06 +/- 0.01 l/kg/h (mean +/- SD), respectively. Mean residence time determined by statistical moment theory of the oral data was different (P less than 0.05) for the immediate-release aminophylline (13.8 +/- 2.8 h) and sustained-release theophylline (18.2 +/- 2.3 h) formulation. Immediate-release aminophylline tablets quickly achieved peak theophylline plasma concentration of 11.51 +/- 1.4 micrograms/ml at 1.6 +/- 0.6 h while the sustained-release theophylline tablets were more slowly absorbed and achieved peak theophylline concentrations of 17.20 +/- 1.3 micrograms/ml at 7.3 +/- 1.0 h. Absolute bioavailability was 87% for the immediate-release and 97% for the sustained-release formulation. Using the principle of superposition, a loading dose of 20 mg/kg of the sustained-release formulation followed by maintenance doses of 15 mg/kg every 24 h was predicted to achieve trough-peak theophylline plasma concentrations between 6 and 17 micrograms/ml.  相似文献   

5.
The pharmacokinetic properties of difloxacin following intravenous (i.v.) and intramuscular (i.m.) administration in goats were investigated. Difloxacin was administered in a single dose of 5 mg/kg body weight for both routes and was assayed in biological fluids (serum and urine) to determine its concentrations, kinetic behaviour and systemic availability. Following a single i.v. injection, the serum difloxacin level was best approximated to follow a two-compartment open model using weighted non-linear regression analysis. The elimination half-life (t1/2 beta) was 6.3 +/- 0.11 h. The volume of distribution at steady-state (Vdss) was 1.1 +/- 0.012 L/kg and the total body clearance (Cltot) was 0.13 +/- 0.001 L/kg/h. Following a single i.m. administration, difloxacin was rapidly absorbed and the mean peak serum concentration (4.1 +/- 0.23 micrograms/ml) was achieved 1 h post administration. The extent of serum protein binding of difloxacin in goats was 13.79 +/- 1.02% and the systemic availability was 95.4 +/- 1.17%. Following i.m. injection of difloxacin at a dose rate of 5 mg/kg b.wt for 5 consecutive days, the drug could not be detected in serum and urine at 4th day from the last injection.  相似文献   

6.
The single-dose disposition kinetics of florfenicol was determined in healthy, non-lactating Egyptian goats, after its intravenous (i.v.) and intramuscular (i.m.) administration at 20 mg kg-1 b.wt. Drug concentrations in serum and urine were determined using microbiological assay method and data was subjected to a kinetic analysis. Florfenicol concentrations in serum decreased in a bi-exponential manner after intravenous administration with distribution (t1/2 alpha) and elimination (t1/2 beta) half-lives of 10.256 +/- 0.938 and 56.237 +/- 3.102 minute, respectively. The steady-state volume of distribution (Vdss) and total body clearance (Cltot) were 3.413 +/- 0.304 l kg-1 and 3.306 +/- 0.333 l kg h-1. After intramuscular administration, the peak serum concentration (Cmax) was 0.859 +/- 0.025 micrograms ml-1, achieved at (Tmax) 1.220 + 0.045 h. Florfenicol was detected in urine up to 24 and 96 hour after i.v. and i.m. administration, respectively. The extent of the protein binding and systemic bioavailability of florfenicol were 22.45 +/- 1.727% and 65.718 +/- 3.372%, respectively.  相似文献   

7.
Six mature Holstein bulls were given an 8-day course of phenylbutazone (PBZ) orally (loading dose, 12 mg of PBZ/kg of body weight and 7 maintenance doses of 6 mg of PBZ/kg, q 24 h). Plasma concentration-vs-time data were analyzed, using nonlinear regression modeling. The harmonic mean +/- pseudo-SD of the biologic half-life of PBZ was 61.8 +/- 12.8 hours. The arithmetic mean +/- SEM of the total body clearance and apparent volume of distribution were 0.0021 +/- 0.0001 L/h/kg and 0.201 +/- 0.009 L/kg, respectively. The predicted mean minimal plasma concentration of PBZ with this dosage regimen was 75.06 +/- 4.05 micrograms/ml. The predicted minimal plasma drug concentration was compared with the observed minimal plasma drug concentration in another group of bulls treated with PBZ for at least 60 days. Sixteen mature Holstein bulls were given approximately 6 mg of PBZ/kg, PO, daily for various musculoskeletal disorders. The mean observed minimal plasma concentration of PBZ in the 16 bulls was 76.10 +/- 2.04 micrograms/ml, whereas the mean predicted minimal plasma concentration was 74.69 +/- 3.10 micrograms/ml. Dosages of 4 to 6 mg of PBZ/kg, q 24 h, or 10 to 14 mg of PBZ/kg, q 48 h, provided therapeutic plasma concentrations of PBZ with minimal steady-state concentrations between 50 and 70 micrograms/ml.  相似文献   

8.
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   

9.
Pharmacokinetic profile and therapeutic range of plasma quinidine concentration were determined in dairy Holstein cows. Plasma half-life of intravenous quinidine was 1.28 +/- 0.492 (0.41-1.65) hr. The pattern of plasma quinidine transition after oral administration varied greatly among individuals. Total body clearance was 58.7 +/- 24.49 ml/min/kg, although renal quinidine clearance was 0.76 +/- 0.441 ml/min/kg. Therefore, the involvement of some extrarenal organ as the main site of excretion was suspected. Seven cows, diagnosed as atrial fibrillation or ventricular premature contraction, were orally administered with quinidine at various dosages. They showed plasma concentration of 2.3 +/- 1.59 mg/l when therapeutic effect was observed. Clinical signs of intoxication were observed at plasma quinidine concentrations over 10 mg/l. These results suggest the difficulty with the maintenance of effective plasma quinidine concentration by an oral or a single intravenous administration, and thus it is concluded that use of quinidine for treatment arrhythmic cows must be carefully done in order to avoid possible intoxication.  相似文献   

10.
The glomerular filtration rate (GFR) was estimated in eight full-term neonatal foals by the single injection inulin plasma clearance method at two days of age, the continuous infusion plasma and urinary clearance methods at three days of age, and the 12-hour endogenous creatinine clearance method at four days of age. The effective renal plasma flow (ERPF) was estimated simultaneously by the single injection para-aminohippuric acid (PAH) plasma clearance method in the eight two-day old foals and the continuous PAH infusion plasma and urinary clearance method in the eight three-day old foals. The GFR (+/- 1 SEM), as determined from the single injection plasma clearance method, was 2.30 +/- 0.34 mL/kg/min; by continuous infusion plasma clearance 2.56 +/- 0.30 mL/kg/min; by continuous infusion urinary clearance 2.82 +/- 0.32 mL/kg/min; and by 12-hour endogenous creatinine clearance 2.81 +/- 0.55 mL/kg/min. Effective renal plasma flow (+/- 1 SEM) measured by the single injection plasma clearance method was 15.22 +/- 1.5 mL/kg/min, by continuous infusion plasma clearance was 18.21 +/- 2.0 mL/kg/min. and by continuous infusion urinary clearance it was 11.95 +/- 1.9 mL/kg/min. The results of these methods were not statistically different. On a per kilogram body weight basis, the full-term neonatal foal's GFR and ERPF was determined to be comparable with adult equine GFR and ERPF.  相似文献   

11.
The pharmacokinetics of amikacin were studied in healthy mature female chickens (n = 6). Single doses of amikacin were injected as an i.v. bolus (10 mg/kg) and i.m. (20 mg/kg) into the same birds with a 30-day rest period between treatments. Amikacin was determined by the fluorescence polarization immunoassay method. The i.v. pharmacokinetics could be described by a two-compartment model with a t1/2 alpha of 0.150 +/- 0.064 h and a t1/2 beta of 1.44 +/- 0.34 h. The total body clearance was 0.109 +/- 0.017 1/h/kg and the volume of distribution at steady-state was 0.193 +/- 0.060 l/kg. Following a single i.m. injection, the peak plasma concentration (Cmax) was 50.79 +/- 4.05 micrograms/ml and occurred at 0.50 +/- 0.26 h. The i.m. extent of absorption was 91.2 +/- 17.6%. Simultaneous modeling of i.v. and i.m. results provided estimates of an absorption half-life of 0.480 +/- 0.158 h. The i.m. pharmacokinetics after repeated administration were studied following the tenth dose (20 mg/kg, every 8 h). The Cssmax was 38.58 +/- 6.96 micrograms/ml and occurred at 0.79 +/- 0.37 h, and the biological half-life of amikacin was 1.86 +/- 0.47 h. The multiple dosing yielded peak concentrations of 39 micrograms/ml and trough concentrations of 3.26 micrograms/ml. Based on these data, the recommended amikacin dosage in chickens is 20 mg/kg body weight every 8 h.  相似文献   

12.
Concentrations of the potent diuretic bumetanide were determined by a sensitive high performance liquid chromatographic procedure in plasma and urine from horses following intravenous and intramuscular administration of a dose rate of 15 micrograms/kg. The elimination half-life was found to be 6.3 min, the volume of distribution at steady state 68 ml/kg and the total plasma clearance 10.9 ml/min/kg. The onset of diuresis occurred within 15 min and diuresis was no longer apparent 1 h after i.v. administration. Given by the intramuscular (i.m.) route, bumetanide was rapidly absorbed; bioavailability was 70-80%. i.m. administration of bumetanide prolonged its plasma half-life (11-27 min) and enhanced and prolonged its diuretic effect.  相似文献   

13.

Introduction

Diuretic failure is a potential life-ending event but is unpredictable and poorly understood. The objectives of this study were to evaluate pharmacodynamic markers of furosemide-induced diuresis and to investigate mechanisms of diuretic braking in dogs receiving constant rate infusion (CRI) of furosemide.

Animals

Six healthy male dogs.

Methods

Raw data and stored samples from one arm of a previously published study were further analyzed to mechanistically investigate causes of diuretic braking in these dogs. Urine volume was recorded hourly during a 5-h furosemide CRI. Urine and blood samples were collected hourly to measure serum and urine electrolytes, urine aldosterone, and plasma and urine furosemide. Serum electrolyte fractional excretion was calculated. Urine sodium concentration was indexed to urine potassium (uNa:uK) and urine furosemide (uNa:uFur) concentrations, plasma furosemide concentration was indexed to urine furosemide concentration (pFur:uFur), and urine aldosterone was indexed to urine creatinine (UAldo:C). Temporal change and the relationship to urine volume were evaluated for these measured and calculated variables.

Results

Urine volume was significantly correlated with urine electrolyte amounts and with uNa:uK. The ratio of pFur:uFur decreased during the infusion, whereas furosemide excretion was unchanged.

Conclusions

There was a strong relationship between urine volume and absolute urine electrolyte excretion. Urine volume was strongly correlated to uNa:uK, giving it potential as a spot indicator of urine production during diuresis. The decrease in uNa:uK over time during the infusion is consistent with mineralocorticoid modification of urinary electrolyte excretion, supporting renin–angiotensin–aldosterone activation as a cause of diuretic braking in this model.  相似文献   

14.
Pharmacokinetics and urinary excretion of sulphadimidine (SDI) were determined in buffalo calves following single oral administration (150 mg/kg). The plasma levels of free sulphadimidine were above minimum effective therapeutic concentration (> 40 micrograms/ml) between 4 and 12 h and the N4-acetylated form of the drug was in the range of 7.2-19.3%. Kinetic evaluation of plasma levels was performed using a two-compartment open model. The absorption and elimination half-lives of SDI were 3.01 and 11.94 h, respectively. Based on this study, an optimal dosage regimen of sulphadimidine in buffalo calves would be 100 mg/kg, followed by 50 mg/kg at 12 h intervals. Sulphadimidine was mainly excreted in the urine as free amine. The percentage of N4-acetyl sulphadimidine in urine was comparatively higher than in plasma.  相似文献   

15.
The disposition of albendazole in sheep   总被引：5，自引：1，他引：4  
Albendazole (ABZ) was administered intraruminally at 4.75 mg/kg to sheep fitted with a permanent bile-duct cannula to determine if its metabolites might contribute to its flukicidal action. ABZ metabolism was consistent with first-pass clearance by the liver, resulting in ABZ sulphoxide (ABZ-SO) and ABZ sulphone (ABZ-SO2) being present in plasma at maximum concentrations (mean Cmax +/- SD) of 2.0 +/- 0.2 micrograms/ml and 0.4 +/- 0.1 micrograms/ml after 8 +/- 3 h and 24 +/- 5 h, respectively. ABZ-SO, but more particularly ABZ-SO2, appeared to bind to plasma proteins but their clearance rates from plasma were similar. Biliary ABZ metabolites were mainly unconjugated ABZ-SO and 2OH-ABZ-SO (8.0% dose) or conjugated glucuronide and sulphate esters (6.3% dose) mainly of 2OH-ABZ-SO and 2OH-ABZ-SO2. The concentration of the major biliary metabolite, unconjugated ABZ-SO, followed a similar time profile to that of ABZ-SO in plasma except that Cmax was much higher (6.2 +/- 2.2 micrograms/ml). Intraruminal administration of ABZ reduced bile flow rate by 30% which may be attributable to an inhibitory effect of ABZ on microtubule formation in hepatic secretory cells. It is suggested that ABZ is sequestered in the liver. This is unlikely to contribute to its flukicidal action, which is probably attributable to ingestion of ABZ-SO from bile and blood by the fluke.  相似文献   

16.
The pharmacokinetics of the novel cephalosporin cefovecin were investigated in a series of in vivo, ex vivo and in vitro studies following administration to adult cats at 8 mg/kg bodyweight. Bioavailability and pharmacokinetic parameters were determined in a cross-over study after intravenous (i.v.) and subcutaneous (s.c.) injections. [14C]cefovecin was used to evaluate excretion for 21 days after s.c. administration. Protein binding was determined in vitro in feline plasma and ex vivo in transudate from cats surgically implanted with tissue chambers. After s.c. administration, cefovecin was characterized by rapid absorption with mean peak plasma concentrations of 141+/-12 microg/mL being achieved within 2 h of s.c. injection with full bioavailability (99%). The mean elimination half-life was 166+/-18 h. After i.v. administration, volume of distribution was 0.09+/-0.01 L/kg and mean plasma clearance was 0.35+/-0.04 mL/h/kg. Approximately 50% of the administered radiolabelled dose was eliminated over the 21-day postdose period via urinary excretion and up to approximately 25% in faeces. In vitro and ex vivo plasma protein binding ranged from 99.8% to 99.5% over the plasma concentration range 10-100 microg/mL. Ex vivo protein binding in transudate was as low as 90.7%. From 8 h postdose, concentrations of unbound (free) cefovecin in transudate were consistently higher than in plasma, with mean unbound cefovecin concentrations being maintained above 0.06 microg/mL (MIC90 of Pasteurella multocida) in transudate for at least 14 days postdose. The slow elimination and long-lasting free concentrations in extracellular fluid are desirable pharmacokinetic attributes for an antimicrobial with a 14-day dosing interval.  相似文献   

17.
Pharmacokinetics of cefotaxime in the domestic cat   总被引：1，自引：0，他引：1  
Cefotaxime was administered as single IV or IM dose for the purpose of examining its pharmacokinetics in healthy cats. The mean predicted plasma concentration of cefotaxime in 6 cats at 0 time after a single IV dosage of 10 mg/kg of body weight was 88.9 micrograms/ml. The mean plasma concentrations decreased to 10.8 micrograms/ml at 2 hours, 3.7 micrograms/ml at 3 hours, and 0.5 microgram/ml at 6 hours. The half-life was 0.98 +/- 0.25 hour (mean +/- SD), and the total body clearance was determined to be 2.76 +/- 1.25 ml/min/kg. After a single IM injection of 10 mg/kg of body weight, the mean maximum observed plasma concentration was 36.2 micrograms/ml at 0.75 hour. The mean absorption half-life was 0.24 hour. In 2 animals, the bioavailability of an IM injection was 98.2% and 93.0%.  相似文献   

18.
Endogenous creatinine clearance and renal excretion of phenylbutazone, osmotically active material, and compounds contributing to the urinary refractive index were studied in 12 Thoroughbred mares after no treatment, after water administration, or after furosemide administration. Urine was quantitatively collected, using urinary bladder catheters. On average, urine flow of the mares was 9 microliters/min/kg without treatment and increased to about 50 microliters/min/kg after water administration and to about 70 microliters/min/kg after furosemide administration. Water administration increased creatinine clearance values and excretion of phenylbutazone. Furosemide administration increased urinary excretion of osmotically active compounds and compounds contributing to urinary refractive index and decreased excretion of phenylbutazone.  相似文献   

19.
In this study pharmacokinetic data for the unfractionated heparin Liquemin were obtained after intravenous and subcutaneous application. Each dosage was examined in 5 healthy, adult Beagle dogs. After intravenous application of 25, 50 and 100 I.U./kg body weight heparin plasma activity of 0.65 +/- 0.15 I.U./ml (mean +/- s), 0.91 +/- 0.10 I.U./ml and 1.94 +/- 0.22 I.U./ml was measured. Subcutaneous applications of 250, 500 or 750 I.U./kg revealed maximum plasma heparin activities of 0.25 +/- 0.10, 0.60 +/- 0.15 and 1.29 +/- 0.24 I.U./ml. The maximum heparin activity in the plasma was observed after 3.8 +/- 1.1 (250 und 500 I.E./kg) or 4.0 +/- 1.0 hours (750 I.E./kg), respectively. Intravenously applicated heparin has a short terminal half-life time (t50) between 22 and 44 minutes. The t50 after subcutaneous application of heparin was distinctly longer. After 250, 500 or 750 I.U./kg the t50 was 3.7 +/- 2.4, 3.5 +/- 1.2 or 5.3 +/- 2.4 hours. Corresponding to this result a lower total clearance (Cltot) was found with increasing doses. Especially the Cltot after subcutaneous injection decreased from 2.08 +/- 0.73 ml/min/kg (250 I.E./kg) to 0.83 +/- 0.27 ml/min/kg (750 I.E./kg). The volume of distribution of heparin corresponded approximately to the plasma volume. The total bioavailability of subcutaneously administered UFH was 53-100% depending on the dosage.  相似文献   

20.
Pharmacokinetic studies of cimetidine hydrochloride in adult horses   总被引：1，自引：0，他引：1  
Histamine type II (H2) antagonists inhibit gastric acid secretion and are useful in treating gastric and duodenal ulcer disease. To provide some information on the pharmacokinetics of the H2 antagonist cimetidine, adult horses were given 3.3 mg/kg cimetidine intravenously (iv) or 3.3 and 10 mg/kg orally. Plasma cimetidine concentrations after 3.3 mg/kg orally were too low to measure. Following 3.3 mg/kg iv, cimetidine displayed two-compartment characteristics with a t1/2 of 0.083 +/- 0.039 h and t1/2 of 2.23 +/- 0.64 h. The total body clearance was 0.443 +/- 0.160 litre/h/kg and the mean residence time was 2.74 +/- 1.11 h. This clearance and t1/2 are similar to that in man. The volume of distribution (Vss) and volume of the central compartment (Vc) were 1.138 +/- 0.230 and 0.276 +/- 0.102 litre/kg, respectively. After a single oral dose of 10 mg/kg as crushed tablets, peak plasma concentration of 1.81 +/- 0.82 micrograms/ml occurred at approximately 1.4 h. Oral absorption of cimetidine appeared variable and slow with an extent of absorption of 0.296 +/- 0.183 and a mean residence time for absorption of 1.99 +/- 0.79 h. This was less than in man. Based on a desired average steady state plasma concentration of 1.0 microgram/ml, 11.0 mg/kg/day iv and 48 mg/kg/day orally can be recommended in adult horses.  相似文献   

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