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1.
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   

2.
The pharmacokinetics of oxytetracycline (OTC) in three weaned piglets was studied following three routes of administration: intravenously, orally as drench, both at a dose of 20 mg/kg, and orally as medicated (400 ppm OTC) pelleted feed administered during 3 consecutive days. Analysis of the intravenous data according to the three compartment pharmacokinetic model revealed that OTC was well distributed in the body (Vf: 1.62 l/kg), had an overall body clearance of 0.25 litre/kg/h, and the elimination half-lives were in the range between 11.6 and 17.2 hrs. The mean OTC binding to plasma proteins was 75.5 +/- 4%. Following the drench route of administration the maximum plasma OTC concentration was achieved between 1 and 5 h post application and ranged between 1.18 and 1.41 micrograms/ml. The mean maximum plasma OTC concentration during medicated feed administration was 0.20 +/- 0.06 microgram/ml, which was achieved approximately 30 hours after the onset of the administration. A steady state OTC plasma level (approximately 0.2 microgram/ml) was maintained till the end of the trial. Within 48 hours after cessation of medicated feed administration the plasma OTC levels were beneath 0.06 microgram/ml. The mean OTC bioavailabilities of the oral routes were low: after the drench route of administration 9.0 +/- 0.67%, and after medicated pelleted feed administration 3.69 +/- 0.8%. The mean OTC renal clearances of each piglet ranged between 10.1 and 13.9 ml/min/kg (based on free OTC plasma fractions). The renal OTC clearance values were urine flow dependent in all piglets and significantly correlated with the renal creatinine clearance (P less than 0.005), being 3-5 times higher than the latter. It is concluded that in piglets OTC is excreted mainly by glomerular filtration and partly by tubular secretion. The potential clinical efficacy of 400 ppm OTC as medicated feed with respect to treatment, e.g. atrophic rhinitis, is discussed.  相似文献   

3.
Summary

The pharmacokinetics of oxytetracycline (OTC) in three weaned piglets was studied following three routes of administration: intravenously, orally as drench, both at a dose of 20 mg/kg, and orally as medicated (400 ppm OTC) pelleted feed administered during 3 consecutive days. Analysis of the intravenous data according to the three compartment pharmacokinetic model revealed that OTC was well distributed in the body (Vie 1.621/kg), had an overall body clearance of 0.25 litre/kg/h, and the elimination half‐lives were in the range between 11.6 and 17.2 hrs.

The mean OTC binding to plasma proteins was 75.5 ± 4%. Following the drench route of administration the maximum plasma OTC concentration was achieved between 1 and 5 h post application and ranged between 1.18 and 1.41 μg/ml. The mean maximum plasma OTC concentration during medicated feed administration was 0.20 ± 0.06 μg/ml, which was achieved approximately 30 hours after the onset of the administration. A steady state OTC plasma level (approximately 0.2 μg/ml) was maintained till the end of the trial. Within 48 hours after cessation of medicated feed administration the plasma OTC levels were beneath 0.06 μg/ml. The mean OTC bioavailabilities of the oral routes were low: after the drench route of administration 9.0 ± 0.67%, and after medicated pelleted feed administration 3.69 ± 0.8%.

The mean OTC renal clearances of each piglet ranged between 10.1 and 13.9 ml/min/kg (based on free OTC plasma fractions). The renal OTC clearance values were urine flow dependent in all piglets and significantly correlated with the renal creatinine clearance (P< 0.005), being 3–5 times higher than the latter. It is concluded that in piglets OTC is excreted mainly by glomerular filtration and partly by tubular secretion. The potential clinical efficacy of 400 ppm OTC as medicated feed with respect to treatment, e.g. atrophic rhinitis, is discussed.  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.
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   

6.
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   

7.
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   

8.
The kinetics of sulphamethoxazole (SMZ) in plasma and milk, and its metabolism, protein binding and renal clearance were studied in three newborn calves and two dairy cows after intravenous administration. SMZ was predominantly acetylated; no hydroxy and glucuronide derivatives could be detected in plasma and urine. Age-dependent pharmacokinetics and metabolism of SMZ were observed. The plasma concentration-time curves of the N4-acetyl metabolite in the elimination phase were parallel to those of the parent drug; the N4-acetyl metabolite plasma percentage depended on age and ranged between 100% (new-born) to 24.5% (cow). SMZ was rapidly eliminated (elimination half-lives: 2.0-4.7 h) and exhibited a relatively small distribution volume (VDarea: 0.44-0.57 l/kg). SMZ was excreted predominantly by glomerular filtration, while its N4-acetyl metabolite was actively eliminated by tubular secretion.  相似文献   

9.
Pharmacokinetics of oxytetracycline (OTC) were studied in 4 cows after administration of either a conventional (OTC-C) or a long-acting (OTC-LA) preparation. After intravenous administration of OTG-G the elimination half-life for OTG was found to be 6 h. Intramuscular injection of OTC-C and OTC-LA resulted in almost identical plasma concentrations of OTC with peak values after 6–8 h. For both preparations the bioavailability after i.m. administration was 100 % and about 60 % of the dose was excreted in the urine during the first week. Plasma concentrations above 0.5 μg/ml were with both preparations maintained for approximately 60 h, indicating no retard effect of OTC-LA as compared to OTC-C.Key words: Oxytetracycline, pharmacokinetics, cattle  相似文献   

10.
The pharmacokinetics of butorphanol tartrate were investigated following intravenous administration of 0.25 mg/kg of body weight to six healthy non-lactating Jersey cows. Three lactating Holstein cows also received 0.045 mg of butorphanol/kg of body weight intravenously to determine the extent and duration of drug transfer into milk. A radioimmunoassay technique was used to measure butorphanol concentrations in plasma and milk. The disposition of butorphanol following intravenous administration was characterized by rapid and extensive distribution followed by a slower elimination phase. Apparent volume of distribution was 4.178 ± 1.145 (mean ± SD) I/kg, mean elimination half-life was 82 min, and clearance was 34.6 ± 7.7 ml/min/kg. Trace quantities of butorphanol were detected in the cow's milk for up to 36 h following administration. These pharmacokinetic data were compared with pharmaco-kinetic and pharmacodynamic data for butorphanol in other species and for three other potent opioids in related ruminant species.  相似文献   

11.
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   

12.
Oxytetracycline (OTC) concentrations on plasma and milk of dairy cows were determined following a single intramuscular injection of five oxytetracycline-20% formulations at a dosage of approximately 10 mg/kg. For obtaining pharmacokinetic reference parameters, one 10% OTC formulation was administered intravenously. The five 20% formulations were compared and evaluated pharmacokinetically with respect to absorption rate, peak plasma and milk OTC concentrations, biological half-life, and relative bioavailability. The mean maximum plasma OTC concentrations varied between 4.5 and 6.8 micrograms/ml and were achieved between 5 and 10 h p.i., depending on the formulation involved. The mean maximum milk concentrations, ranging from 1.12 to 1.92 micrograms/ml, were achieved 12 to 24 h p.i. A plasma OTC concentration exceeding 0.5 microgram/ml was maintained for 48 h to 70 h, and in milk for 33 to 49 h, depending on the formulation involved. Formulations exhibiting the lowest clinically noticeable irritation showed the highest peak plasma OTC concentrations and the best bioavailability. Among the formulations the calculated withholding periods for milk were in the range of 3 to 4 days and for edible tissues of 9 to 14 days. The OTC and creatinine clearances were significantly correlated to each other and to the urinary flow. OTC was excreted predominantly by glomerular filtration, partly by tubular secretion minus urogenital (distal renal tubuli and bladder) reabsorption.  相似文献   

13.
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   

14.
Summary

Oxytetracycline (OTC) concentrations in plasma and milk of dairy cows were determined following a single intramuscular injection of five oxytetracycline‐20% formulations at a dosage of approximately 10 mg/kg. For obtaining pharmacokinetic reference parameters, one 10% OTC formulation was administered intravenously. The five 20% formulations were compared and evaluated pharmacokinetically with respect to absorption rate, peak plasma and milk OTC concentrations, biological half‐life, and relative bioavailability. The mean maximum plasma OTC concentrations varied between 4.5 and 6.8 μg/ml and were achieved between 5 and 10 h p.i., depending on the formulation involved. The mean maximum milk concentrations, ranging from 1.12 to 1.92 μg/ml, were achieved 12 to 24 h p.i. A plasma OTC concentration exceeding 0.5 μg/ml was maintained for 48 h to 70 h, and in milk for 33 to 49 h, depending on the formulation involved.

Formulations exhibiting the lowest clinically noticeable irritation showed the highest peak plasma OTC concentrations and the best bioavailability. Among the formulations the calculated withholding periods for milk were in the range of 3 to 4 days and for edible tissues of 9 to 14 days. The OTC and creatinine clearances were significantly correlated to each other and to the urinary flow. OTC was excreted predominantly by glomerular filtration, partly by tubular secretion minus urogenital (distal renal tubuli and bladder) reabsorption.  相似文献   

15.
Summary

The kinetics of sulphamethoxazole (SMZ) in plasma and milk, and its metabolism, protein binding and renal clearance were studied in three newborn calves and two dairy cows after intravenous administration. SMZ was predominantly acetylated; no hydroxy and glucuronide derivatives could be detected in plasma and urine. Age‐dependent pharmacokinetics and metabolism of SMZ were observed. The plasma concentration‐time curves of the N4‐acetyl metabolite in the elimination phase were parallel to those of the parent drug; the N4‐acetyl metabolite plasma percentage depended on age and ranged between 100% (new‐born) to 24.5% (cow). SMZ was rapidly eliminated (elimination half‐lives: 2.0–4.7 h) and exhibited a relatively small distribution volume (VDarea: 0.44–0.57 l/kg). SMZ was excreted predominantly by glomerular filtration, while its N4‐acetyl metabolite was actively eliminated by tubular secretion.  相似文献   

16.
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   

17.
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   

18.
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   

19.
Gossypol pharmacokinetics in mid-lactation Brown swiss dairy cows   总被引：1，自引：0，他引：1  
A bolus equivalent to 450 ppm (dosage based on average feed intake for lactating dairy cows of similar mass) of gossypol was administered orally to three Brown Swiss dairy cows in mid lactation daily for a 7-day treatment period. Blood samples were taken daily during a 2-day pretreatment period, the 7-day treatment period and a 6-day recovery period. The serum recovered from the cows was stored at -20°C until analysis for extractable gossypol content. The highest concentration of gossypol (a mean of 0.53 g/ml serum) was attained in all the cows on day 6 of the treatment period, indicating that a steady-state condition had been reached before the end of the treatment period. The gossypol concentrations then gradually declined during the 6-day recovery period but never fell to the zero baseline. The cows exhibited terminal elimination half-lives of 67, 67.5 and 40 h. Gossypol elimination was best described by a bi-exponential decay curve in two cows and a mono-exponential decay curve in the remaining cow.  相似文献   

20.
The absorption, metabolism and urinary excretion of phenylbutazone were investigated in six adult cattle in a cross-over study involving administration intravenously, intramuscularly and orally at a dose rate of 4.4 mg kg-1. Following intravenous injection plasma disposition was described by a three compartment open model with mean elimination half-life (t1/2 beta) and clearance (ClB) values of 35.9 hours and 2.77 ml kg-1 h-1, respectively. Somewhat longer t1/2 beta values were obtained after oral and intramuscular dosing and these may have resulted from sequestration within and slow absorption from the gastrointestinal tract and continual uptake from intramuscular sites following precipitation as a depot. Absorption was more complete after intramuscular than after oral dosing; area under curve values were almost twice as high for the intramuscular route. Double peaks in the plasma concentration time curves after oral dosing were recorded in some cows. These may have resulted from drug adsorption on to and subsequent desorption from hay or as a consequence of enterohepatic shunting. There was no evidence for opening of the oesophageal groove and direct passage of the drug into the abomasum. Two hydroxylated metabolites of phenylbutazone, oxyphenbutazone and gamma-hydroxyphenylbutazone were detected in trace amounts in plasma for 72 hours and in much higher concentrations in urine for 168 hours. Approximate urine:plasma (U/P) concentration ratios for the metabolites approached and occasionally exceeded the U/P ratio for endogenous creatinine, indicating poor reabsorption and, possibly, tubular secretion. Cumulative urinary excretion data indicated that the hydroxylated derivatives of phenylbutazone are probably formed more slowly in cattle than in horses.  相似文献   

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