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1.
Pharmacokinetics and bioavailability of cephalothin in horse mares   总被引：1，自引：0，他引：1  
The pharmacokinetics and bioavailability of cephalothin given to 6 horse mares at a dosage level of 11 mg/kg of body weight IV or IM were investigated. The disposition of cephalothin given IV was characterized by a rapid disposition phase with a mean half-life of 2.89 minutes and a subsequent slower elimination phase with a mean half-life of only 14.7 minutes. The mean residence time of cephalothin was 10.6 +/- 2.11 minutes. The total plasma clearance of cephalothin averaged 13.6 ml/min/kg and was caused by metabolism and renal elimination. Renal clearance of cephalothin averaged 1.32 ml/min/kg and accounted for elimination of about 10.1% of the administered dose. The volume of distribution at steady state averaged 151 mg/kg. Plasma protein binding of cephalothin at a concentration of 10 micrograms/ml averaged 17.9 +/- 2.5%. Cephalothin was rapidly metabolized to desacetylcephalothin. Maximum plasma desacetylcephalothin concentrations were observed in the blood samples collected 5 minutes after IV doses and averaged 22.9 micrograms/ml. The apparent half-life of desacetylcephalothin in plasma was 41.6 minutes and its renal clearance averaged 4.49 +/- 2.43 ml/min/kg. An average of 33.9% of the dose was recovered in the urine as desacetylcephalothin. The maximum plasma cephalothin concentration after IM administration was 11.3 +/- 3.71 micrograms/ml. The terminal half-life was 47.0 minutes and was longer than the half-life after IV administration. The bioavailability of cephalothin given IM ranged from 38.3% to 93.1% and averaged 65.0 +/- 20.5%.  相似文献   

2.
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   

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.
A single oral dosage of furaltadone and nitrofurazone (14.0 mg/kg) to 5 preruminant calves (in a cross-over trial) revealed mean maximum plasma concentration of 2.5 and 3.5 microgram/ml, respectively, at approximately 3 h after administration. The final elimination half-lives of furaltadone and nitrofurazone were 2.5 and 5 h, respectively. Urinary recovery of these two nitrofurans in 3 calves revealed approximately 2% of the orally administered dose. The renal clearance of the unbound drugs did not differ (for both drugs approximately 0.42 ml/min/kg); furaltadone clearance was strongly related to urine flow.  相似文献   

5.
Amikacin, an aminoglycoside antimicrobial, was administered to a killer whale (Orcinus orca) and a beluga whale (Delphinapterus leucas) for the treatment of clinical signs consistent with gram-negative aerobic bacterial infections. Dosage regimens were designed to target a maximal plasma concentration 8-10 times the minimum inhibitory concentrations of the pathogen and to reduce the risk of aminoglycoside toxicity. Allometric analysis of published pharmacokinetic parameters in mature animals yielded a relationship for amikacin's volume of distribution, in milliliters, given by the equation Vd = 151.058(BW)1.043. An initial dose for amikacin was estimated by calculating the volume of distribution and targeted maximal concentration. With this information, dosage regimens for i.m. administration were designed for a killer whale and a beluga whale. Therapeutic drug monitoring was performed on each whale to assess the individual pharmacokinetic parameters. The elimination half-life (5.99 hr), volume of distribution per bioavailability (319 ml/kg). and clearance per bioavailability (0.61 ml/min/kg) were calculated for the killer whale. The elimination half-life (5.03 hr), volume of distribution per bioavailability (229 ml/kg). and clearance per bioavailability (0.53 ml/min/kg) were calculated for the beluga whale. The volume of distribution predicted from the allometric equation for both whales was similar to the calculated pharmacokinetic parameter. Both whales exhibited a prolonged elimination half-life and decreased clearance when compared with other animal species despite normal renal parameters on biochemistry panels. Allometric principles and therapeutic drug monitoring were used to accurately determine the doses in these cases and to avoid toxicity.  相似文献   

6.
Summary

A single oral dosage of furaltadone and nitrofurazone (14.0 mg/kg) to 5 preruminant calves (in a cross‐over trial) revealed mean maximum plasma concentration of 2.5 and 3.5 pg/ml, respectively, at approximately 3 h after administration. The final elimination half‐lives of furaltadone and nitrofurazone were 2.5 and 5 h, respectively.

Urinary recovery of these two nitrofurans in 3 calves revealed approximately 2% of the orally administered dose. The renal clearance of the unbound drugs did not differ (for both drugs approximately 0.42 ml/min/kg);furaltadone clearance was strongly related to urine flow.  相似文献   

7.
A suitable method in the routine veterinary practice for the quantitative determination of the glomerular filtration rate (GFR) in dogs and cats has not been available until to date. Therefore, we modified the known plasma clearance model (=P-CL). The resulting P-CLterminal was assessed concerning its diagnostic value. P-CL of exogenous creatinine (P-CLcrea) and of inulin were determined in dogs (n=12, Beagle, 6 months of age) and cats (n=11, Domestic Short Hair, 14 months of age). The marker substances were administered as a bolus injection. In fasted dogs, P-CLcrea was 84.3 +/- 14.85 ml/min/m2 after a creatinine dose of 2.4 g/m2. An electrolyte infusion during the clearance determination did not alter the resulting values (p>0.05). In fasted cats, P-CLcrea was 54.7 +/- 5.8 ml/min/m2 (creatinine dose 2.0 g/m2). The inulin clearance, determined at the same time, was 104.5 +/- 19.81 ml/min/m2. Feeding the cats just before and during the test increased P-CL of both markers significantly (p<0.05). In order to adapt the clearance method for diagnostic assessment of GFR in the small animal practice, we aimed at minimizing the number of required blood samples (3 instead of 7 or more) and introduced the modified exogenous creatinine clearance (P-CLterminal). These values determined were 108.4 +/- 20.81 ml/min/m2 in fasted dogs and 66.3 +/- 11.81 ml/min/m2 in fasted cats. An electrolyte infusion (dogs) and feeding (cats) had the same effect on P-CLterminal values as described above for P-CL. In conclusion,the modified exogenous creatinine clearance is a suitable renal function test for the early diagnosis of renal disease in dogs and cats presented in small animal practices.  相似文献   

8.
The pharmacokinetics and bioavailability of probenecid given IV and orally at the dosage level of 10 mg/kg of body weight to mares were investigated. Probenecid given IV was characterized by a rapid disposition phase with a mean half-life of 14.0 minutes and a subsequent slower elimination phase with a mean half-life of 87.8 minutes in 5 of 6 mares. In the remaining mare, a rapid disposition phase was not observed, and the half-life of the elimination phase was slower (172 minutes). The mean residence time of probenecid averaged 116 minutes for all 6 mares and 89.2 minutes for the 5 mares with biphasic disposition. The total plasma clearance of probenecid averaged 1.18 +/- 0.49 ml/min/kg, whereas renal clearance accounted for 42.6 +/- 9.3% of the total clearance. The steady-state volume of distribution of probenecid averaged 116 +/- 28.2 ml/kg. Plasma protein binding of probenecid was extensive, with 99.9% of the drug bound at plasma probenecid concentrations of 10 micrograms/ml. The maximum plasma probenecid concentration after 10 mg/kg orally averaged nearly 30 micrograms/ml. The half-life of probenecid after oral administration was approximately 120 minutes. Oral bioavailability was good with greater than 90% of the dose absorbed. The effect of probenecid on tubular secretion of organic anions was evaluated by determining the pharmacokinetics of IV cefazolin (11 mg/kg) administered alone and 15 minutes after probenecid (10 mg/kg orally). Treatment with probenecid did not affect pharmacokinetic values of cefazolin. This failure of probenecid to alter the pharmacokinetics of cefazolin may be caused by insufficient plasma probenecid concentrations after the oral dose.  相似文献   

9.
Following intravenous administration of an oxytetracycline-HC1 and an oxytetracycline-dihydrate formulation to dairy cows, no statistical difference could be found between the pharmacokinetic parameters, derived from the three-compartment model, of these preparations. Urinary recovery was continued for a period of 72 h following intravenous or intramuscular OTC administration. The recovery of OTC in the urine in the 72-h period was in the range of 73% to 96% of the available dose administered. The renal OTC clearance, the renal creatinine clearance, the urinary flow, and the interrelationships of these were determined on the basis of urine and plasma data. The mean OTC renal clearance ranged from 482 to 1050 ml/min and the creatinine clearance from 651 to 1304 ml/min. The OTC and creatinine clearances were significantly correlated to the urine flow up to 30 ml/min. The total body clearance and renal clearance values were of the same order of magnitude, and along with the urine recovery data they provided evidence of predominantly renal route of OTC elimination in dairy cows. The renal OTC elimination is the net result of mainly glomerular filtration, partly tubular secretion, minus reabsorption in the urogenital tract.  相似文献   

10.
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   

11.
1. The pharmacokinetics of sparfloxacin in broiler chicken was investigated following a single intravenous dose of 10 mg/kg and a single oral dose of 20 mg/kg. The pharmacokinetic parameters (AUC(0-24) or C(max)) were integrated with the pharmacodynamic parameter (MIC(90)) to optimize sparfloxacin dosage in chicken. 2. The apparent volume of distribution, total body clearance, mean residence time and elimination half-life following oral administration were 2.411/kg, 4.55 ml/min per kg, 10.54 and 5.94 h, respectively. Oral bioavailability was 61.7%. 3. Sparfloxacin was found to possess clinically useful pharmacokinetic properties. Based on pharmacokinetic/pharmacodynamic integration an oral dose of 20 mg/kg sparfloxacin for every 24 h might be recommended for a successful clinical effect in chickens.  相似文献   

12.
Pharmacokinetics of florfenicol in veal calves   总被引：13，自引：0，他引：13  
The pharmacokinetic disposition of florfenicol was described in veal calves after administration of a single 22-mg/kg dose intravenously, orally after a 12-h fast and orally 5 min post feeding. Both serum concentrations and urinary excretion were studied. After intravenous administration the median elimination half-life was 171.9 min while the half-life of the distribution phase was 5.9 min. The median body clearance (Cl) and apparent volume of distribution (Vz) were 2.85 ml/kg/min and 0.78 l/kg, respectively. Following oral administration the median bio-availability (f) was 0.88 for calves dosed after a 12-h fast and 0.65 for calves dosed 5 min post feeding. Calves given the oral doses had a complex absorption pattern with delayed absorption. Slightly more than 50% of the administered dose both orally and intravenously was recovered as unchanged florfenicol in the urine by 30 h.  相似文献   

13.
Summary

Following intravenous administration of an oxytetracycline‐HC 1 and an oxytetracycline‐dihydrate formulation to dairy cows, no statistical difference could be found between the pharmacokinetic parameters, derived from the three‐compartment model, of these preparations. Urinary recovery was continued for a period of 72 h following intravenous or intramuscular OTC administration.

The recovery of OTC in the urine in the 72‐h period was in the range of 73% to 96% of the available dose administered.

The renal OTC clearance, the renal creatinine clearance, the urinary flow, and the interrelationships of these were determined on the basis of urine and plasma data. The mean OTC renal clearance ranged from 482 to 1050 ml/min and the creatinine clearance from 651 to 1304 ml/min. The OTC and creatinine clearances were significantly correlated to the urine flow up to 30 ml/min. The total body clearance and renal clearance values were of the same order of magnitude, and along with the urine recovery data they provided evidence of predominantly renal route of OTC elimination in dairy cows. The renal OTC elimination is the net result of mainly glomerular filtration, partly tubular secretion, minus reabsorption in the urogenital tract.  相似文献   

14.
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   

15.
Para-aminohippuric acid (PAHA, 0.1 mg/min/kg of body weight) was infused IV into 2 mares, followed by concurrent IV infusion of PAHA and probenecid (0.075, 0.15, 0.25, or 0.35 mg of probenecid/min/kg). Probenecid infusion reduced the clearance of PAHA at serum probenecid concentrations greater than 55 micrograms/ml. At 12-hour intervals, probenecid (in 5 repeated doses - 50, 75, 100, or 200 mg/kg) was administered by gavage to 2 mares. Mean serum probenecid concentration was greater than 55 micrograms/ml for all dosages. At dosages less than 200 mg/kg, accumulation of probenecid in the serum was minimal from the 1st to the 5th dose. At a dosage of 200 mg/kg, probenecid accumulated in the serum from the 1st to the 5th dose. Intragastric administration of 5 doses of probenecid (75 mg/kg) at 12-hour intervals to 6 mares reduced the clearance of PAHA by 50%. Bioavailability of probenecid was 117 and 102% for 2 mares after a single intragastric dose, compared with a single IV dose.  相似文献   

16.
The pharmacokinetic disposition of 2-mercaptopropionylglycine (2-MPG) given as a single intravenous injection and/or as a single oral dose was studied in 9 normal and 13 cystinuric dogs. After intravenous injection of approximately 10 or 20 mg/kg body weight the pharmacokinetics were best described by a three-exponential function. The first phase involved a distribution process apparently including establishment of drug-plasma protein and drug-tissue binding. The second phase involved rapid renal elimination and 60% of the drug was excreted within 3 h of administration. There was also a slow terminal third phase with a long half-life after both intravenous (t1/2 = 23 h) and oral (t1/2 = 22 h) administration. No dose dependency was observed. A deep pool of reversibly tissue-bound 2-MPG was indicated by a Vss of 3.3 +/- 0.9 l/kg body weight and the long terminal elimination phase. Total clearance was estimated as 4.1 +/- 0.9 ml/min/kg body weight. 2-MPG was eliminated mainly by renal excretion, but there was a difference in recovery of dose between normal and cystinuric dogs. During the first 24 h after intravenous and oral administration, 69% and 54%, respectively, of the drug was recovered in the urine of normal dogs. The corresponding figures in cystinuric dogs were 44% and 29%, respectively. The absolute bioavailability (FAUC) was 88 +/- 20% in normal dogs.  相似文献   

17.
Pharmacokinetics and bioavailability of cefazolin in horses   总被引：1，自引：0，他引：1  
The pharmacokinetics and bioavailability of cefazolin given (IV, IM) to horses at the dosage of 11 mg/kg were investigated. The disposition of cefazolin given by IV route was characterized by a rapid disposition phase with a half-life of 5 to 10 minutes and a subsequent slower elimination phase with a half-life of 35 to 46 minutes. The total plasma clearance of cefazolin averaged 5.51 ml/min/kg and was due mainly to renal clearance (5.39 ml/min/kg) of unchanged drug. The volume of distribution at steady-state averaged 188 ml/kg. Plasma protein binding of cefazolin at a concentration of 10 micrograms/ml averaged 8.1 +/- 1.9%. Given by the IM route, cefazolin was rapidly absorbed; the extent of bioavailability was 78.4 +/- 18.8%, and the terminal half-life ranged from 49 to 99 minutes. Thus, cefazolin was extensively absorbed, but was eliminated more slowly than after IV administration.  相似文献   

18.
Excretion of creatinine, sodium sulfanilate (SS), and phenolsulfonphthalein (PSP) was studied in healthy goats. In conscious goats, mean (+/- SEM) inulin clearance was 2.26 +/- 0.08 ml/min/kg of body weight. Endogenous creatinine clearance, 1.97 +/- 0.09 ml/min/kg, underestimated inulin clearance (P less than 0.01), probably because of the presence of noncreatinine chromogens in caprine plasma. The estimated renal clearance of PSP was 6.88 +/- 0.39 ml/min/kg, whereas the estimated renal clearance of SS was 3.71 +/- 0.39 ml/min/kg. Both exceeded inulin clearance (P less than 0.01), confirming renal tubular secretion of both compounds. In 6 anesthetized goats, exogenous creatinine clearance and SS clearance exceeded inulin clearance (P less than 0.05). Results of stop-flow experiments documented secretion of creatinine and SS by the proximal portion of the caprine nephron. Plasma half-life of PSP in uninephrectomized goats exceeded that in intact goats (20.2 +/- 1.5 min vs 11.9 +/- 0.7 min; P less than 0.01). Similarly, plasma half-life of SS was greater in goats after uninephrectomy (58.2 +/- 6.2 min vs 30.4 +/- 1.2 min; P less than 0.01).  相似文献   

19.
The pharmacokinetics of flunixin meglumine in the sheep   总被引：4，自引：0，他引：4  
Flunixin meglumine was administered intravenously and intramuscularly in sheep and the pharmacokinetics of the drug studied. Plasma concentrations of flunixin were measured by high performance liquid chromatography. The decline in plasma- flunixin concentration with time was best fitted by a triexponential equation. The pharmacokinetics following intravenous administration of 1.0 mg/kg indicate that flunixin has a rapid distribution half-life (t½π= 2.3 min), a slow body clearance rate (Clb= 0.6 ml/kg/min) and an elimination half-life of 229 min. Similarly, at 2.0 mg/kg, flunixin is rapidly distributed from the plasma, t½π= 2.7 min, has a slow body clearance rate (C/b = 0.7 mk/lg/min) and an elimination half-life of 205 min.
Following intramuscular injection flunixin is rapidly and well absorbed from the injection site. It had a mean maximum concentration ( C max) of ≫5.9 μg/ml when administered at a dose rate of 1.1 mg/kg, and a relative bioavailability of 70%. Plasma concentrations increase proportionally to dose over the range 1.1 mg/kg-2.2 mg/kg when administered by the intramuscular route.  相似文献   

20.
Pharmacokinetics of cefaronide, ceftriaxone and cefoperazone in sheep   总被引：2，自引：0，他引：2  
The pharmacokinetics of cefaronide (16 gm/kg dose), ceftriaxone and cefoperazone (47 gm/kg dose), after intravenous (i.v.) administration were determined in six Merino ewes. The mean values for terminal half life, steady state volume of distribution Vd(ss), renal clearance (ClR) and total body clearance (ClB) for cefaronide were 1.5 h, 0.39 l/kg, 0.06 l/h/kg and 0.16 l/h/kg, for ceftriaxone; 1.7 h, 0.30 l/kg, 0.08 l/h/kg, and 0.22 l/h/kg, and 0.7 h, 0.16 l/kg, 0.02 l/h/kg and 0.16 l/h/kg for cefoperazone, respectively. After 5.5 h, approximately 42% cefaronide, and after 8 h, approximately 37% ceftriaxone and 13% cefoperazone, was excreted in urine. The non-renal elimination of ceftriaxone and cefoperazone appeared to be more rapid in sheep than is reported in man. Cefaronide was excreted largely unchanged in the urine of sheep. Therefore, the elimination of cefaronide in sheep was similar to that found in man. Cefaronide was well distributed in sheep, whereas ceftriaxone and cefoperazone appeared to be distributed to a lesser degree. These findings underline the different disposition of drugs in different species.  相似文献   

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