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1.
The pharmacokinetics and bioavailability of rifampin were determined after IV (10 mg/kg of body weight) and intragastric (20 mg/kg of body weight) administration to 6 healthy, adult horses. After IV administration, the disposition kinetics of rifampin were best described by a 2-compartment open model. A rapid distribution phase was followed by a slower elimination phase, with a half-life (t1/2[beta]) of 7.27 +/- 1.11 hours. The mean body clearance was 1.49 +/- 0.41 ml/min.kg, and the mean volume of distribution was 932 +/- 292 ml/kg, indicating that rifampin was widely distributed in the body. After intragastric administration of rifampin in aqueous suspension, a brief lag period (0.31 +/- 0.09 hour) was followed by rapid, but incomplete, absorption (t1/2[a] = 0.51 +/- 0.32 hour) and slow elimination (t1/2[d] = 11.50 +/- 1.55 hours). The mean bioavailability (fractional absorption) of the administered dose during the first 24 hours was 53.94 +/- 18.90%, and we estimated that 70.0 +/- 23.6% of the drug would eventually be absorbed. The mean peak plasma rifampin concentration was 13.25 +/- 2.70 micrograms/ml at 2.5 +/- 1.6 hours after dosing. All 6 horses had plasma rifampin concentrations greater than 2 micrograms/ml by 45 minutes after dosing; concentrations greater than 3 micrograms/ml persisted for at least 24 hours. Mean plasma rifampin concentrations at 12 and 24 hours after dosing were 6.86 +/- 1.69 micrograms/ml and 3.83 +/- 0.87 micrograms/ml, respectively. We tested 162 isolates of 16 bacterial species cultured from clinically ill horses for susceptibility to rifampin.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

2.
AIM: To determine the half life (T1/2), time taken to reach maximum plasma concentration (Tmax) and maximum plasma concentration (Cmax) of thalidomide in sheep following I/V, oral and topical treatment with a single dose of thalidomide.

METHOD: Three groups of 4–6-month-old ram lambs were treated with thalidomide dissolved in dimethylsulphoxide (DMSO). The first group (n=10) was treated I/V with 100?mg thalidomide in 2?mL DMSO; the second group (n=8) received 400?mg thalidomide in 2?mL DMSO orally, and the third group (n=8) had 400?mg thalidomide in 4?mL DMSO applied topically. Plasma samples were collected up to 36 hours after treatment, snap-frozen at ?80°C and analysed for concentrations of thalidomide using high performance liquid chromatography.

RESULTS: Following I/V administration, T1/2 was 5.0 (SEM 0.4) hours, volume of distribution was 3,372.0 (SEM 244.3) mL/kg and clearance was 487.1 (SEM 46.1) mL/hour.kg. Topical application of 400?mg thalidomide did not increase plasma concentrations. Following oral administration, thalidomide bioavailability was 89%, with T1/2, Tmax, and Cmax being 7.2 (SEM 0.8) hours, 3.0 (SEM 0.4) hours and 1,767.3 (SEM 178.1) ng/mL, respectively.

CONCLUSION: Topical administration using DMSO as a solvent did not increase concentrations of thalidomide in plasma. The mean pharmacokinetic parameters determined following oral treatment with 400?mg of thalidomide were similar to those reported in humans receiving a single 400?mg oral dose (T1/2 7.3 hours; Tmax 4.3 hours and Cmax 2,820?ng/mL). There is potential for thalidomide to be used as a model for the treatment of chronic inflammatory conditions in sheep, such as Johne's disease, where tumour necrosis factor alpha plays a pathogenic role.  相似文献   

3.
ObjectiveTo evaluate the pharmacokinetics of amitriptyline and its active metabolite nortriptyline after intravenous (IV) and oral amitriptyline administration in healthy dogs.Study designProspective randomized experiment.AnimalsFive healthy Greyhound dogs (three males and two females) aged 2–4 years and weighing 32.5–39.7 kg.MethodsAfter jugular vein catheterization, dogs were administered a single oral or IV dose of amitriptyline (4 mg kg−1). Blood samples were collected at predetermined time points from baseline (0 hours) to 32 hours after administration and plasma concentrations of amitriptyline and nortriptyline were measured by liquid chromatography triple quadrupole mass spectrometry. Non-compartmental pharmacokinetic analyses were performed.ResultsOrally administered amitriptyline was well tolerated, but adverse effects were noted after IV administration. The mean maximum plasma concentration (CMAX) of amitriptyline was 27.4 ng mL−1 at 1 hour and its mean terminal half-life was 4.33 hours following oral amitriptyline. Bioavailability of oral amitriptyline was 6%. The mean CMAX of nortriptyline was 14.4 ng mL−1 at 2.05 hours and its mean terminal half-life was 6.20 hours following oral amitriptyline.Conclusions and clinical relevanceAmitriptyline at 4 mg kg−1 administered orally produced low amitriptyline and nortriptyline plasma concentrations. This brings into question whether the currently recommended oral dose of amitriptyline (1–4 mg kg−1) is appropriate in dogs.  相似文献   

4.
Background: Lactate concentration in blood or plasma ([LAC]) and change in [LAC] are associated with survival in sick foals. Hypothesis: [LAC] and change in [LAC] over time are associated with survival at 96 hours and discharge in neonatal foals. Furthermore [LAC] and change in [LAC] over time correlate with blood culture results and blood pressure at admission. Animals: Two hundred and twenty‐five foals consecutively admitted to a Neonatal Intensive Care Unit. Methods: Retrospective case review. Foals ≤30 days of age with [LAC] from arterial (190) or umbilical (35) blood gas analysis ([LAC]BG) at admission, 24, and 48 hours. [LAC]BG, blood pressure, blood culture status, and outcome (survival versus nonsurvival at 96 hours and discharge) were recorded. Change in [LAC]BG over time ([LAC]BGΔT) was calculated. Results: [LAC]BG was lower in survivors (96 hours and discharge) at all times. [LAC]BGΔT was larger for survivors (96 hours). Odds of survival (96 hours and discharge) decreased 18, 39, 53 and 22, 38, and 47%, respectively, at each sample time for every 1 mmol/L increment in [LAC]BG and increased 156% for each 1.0/day increment in [LAC]BGΔT from admission to 24 hours at 96 hours. Blood pressure and [LAC]BG were not correlated (P= .196) until removal of selected foals (mean arterial pressure <60 mmHg, admission [LAC]BG <5.5 mmol/L) (P < .001). Bacteremia was not associated with [LAC]BG. Proposed admission [LAC]BG cut‐points for future studies were 6.5 mmol/L (96 hours) and 5.5 mmol/L (discharge). Conclusions and Clinical Importance: Prospective studies evaluating [LAC], [LAC]BGΔT, and cut‐points in sick foals are warranted.  相似文献   

5.
The pharmacokinetics of orally administered pefloxacin were studied to evaluate the bio-enhancing effect of the herbal bio-enhancer, trikatu, in mountain Gaddi goats (n = 6). The findings of the study revealed a decreased plasma concentration (p > 0.05) of pefloxacin following trikatu administration during the absorption phase (10, 15, 20 min post pefloxacin administration). In contrast, the plasma concentrations of pefloxacin were significantly higher at 4, 6, 8 and 12 h (during the elimination phase) of the pefloxacin administration. The findings of the investigation revealed higher values for the area under the curve, the area under the first moment of the plasma drug concentration time curve, the mean residential time, the total duration of pharmacological action and bioavailability. Trikatu treatment, however, significantly reduced the elimination half life (t1/2β) and zero time intercept of the elimination phase. The apparent volume of distribution based on the total area under the plasma drug concentration curve [(Vd(area)] and the apparent volume of distribution based on the zero time plasma concentration intercept of the elimination phase [Vd(B)] were significantly higher in trikatu treated animals indicating a better penetration of the drug. Based on the MIC of 0.8 µg/ml of pefloxacin, a priming dose of 6.0 mg/kg and a maintenance dose of 2.21 mg/kg is required to be administered at 8 h intervals. For practical purposes in goats this would mean a priming dose of 6 mg/kg and a maintenance dose of 2 mg/kg given by the oral route, to be repeated at 8 h intervals.  相似文献   

6.
Eltenac (ELT) [4-(2,6-dichlorophenyl)amino-3-thiophene] is a non-steroidal anti-inflammatory drug (NSAID) that was developed for veterinary use in horses and cattle. The pharmacokinetics of ELT was evaluated in horses at 0.5 mg/kg body weight (BW) after single IV injection after 5 days of repeated IV administration and after a single IV injection in horses previously subjected to 250 mg/kg BW of sodium bicarbonate (NaHCO3) as an alkalization treatment. The aim was to determine whether blood and subsequent urinary alkalization could modify the pharmacokinetics of ELT. Drug quantification was performed with serum and urine using high performance liquid chromatography with UV-visible detection. The results were also integrated with cyclo-oxygenase-inhibition literature data to review the dosage scheme of ELT in horses. After a single intravenous administration, ELT was characterized by rapid distribution (mean t½λ1 = 0.18 ± 0.07 hour) and a short elimination half-life (mean t½λ2 = 2.9 ± 0.68 hour). The volume of distribution was small (Vdss = 253.51 ± 47.55 mL/kg), which is likely because of the high percentage of drug protein binding (approximately 97%). The AUC0-∞ and ClB were 6.92 ± 0.84 h*μg/mL and 73.2 ± 10 mL/h/kg, respectively. Repeated administration did not cause either accumulation or modification of the pharmacokinetic profile. The in vitro effective concentrations were maintained for a 6-hour period. The alkalization procedure appeared to accelerate drug elimination, as ELT was quantifiable only for 6 hours; however, the drug clearance was not significantly modified. Thus, the administration of alkaline compounds to accelerate the elimination of ELT is not completely confirmed.  相似文献   

7.
The double-isotope single-injection method to estimate renal function which utilizes the radiolabeled chemicals [131I]sodium iodohippurate and [125I]sodium iothalamate was evaluated in swine. A total of 46 normal, cross-bred swine were used to determine the applicability of this method for measuring the glomerular filtration rate and effective renal plasma flow. The mean glomerular filtration rate in pigs was determined to be 5.33 +/- 0.82 ml/kg of body weight/minute for [125I]sodium iothalamate with a biological half-life (T 1/2) of 39.18 +/- 7.44 minutes. The mean effective renal plasma flow was determined to be 19.25 +/- 3.12 ml/kg of body weight/minute for [313I]sodium iodohippurate, with a T 1/2 of 18.45 +/- 1.74 minutes. These values are more closely related to the glomerular filtration and effective renal plasma flow values reported for dogs and cats than they are to values reported for man. The method is rapid and reliable; results are available 6 to 8 hours after the experiment. This method is advantageous when information about renal function variables is a prerequisite to pharmacokinetic or toxicologic studies.  相似文献   

8.
The current study was conducted to evaluate daily within-horse variation of plasma alpha-tocopherol concentration (TOC) (Experiment 1 [EXPT1]) and to determine the effect of a single meal on plasma TOC (Experiment 2 [EXPT2]). In EXPT1, venous jugular blood samples were collected from four pregnant (6–7 months of gestation), light horse mares (8.8 ± 2.9 years of age, mean ± SD; range, 5–11 years of age) between 7:30 AM and 8:30 AM, followed by eight hourly samples, and analyzed for plasma TOC. All horses were fed 5 kg dry matter (DM) grass hay 18 hours before sample collection and received no additional feed during the sampling period. Mean within-horse coefficient of variation for TOC was 3.5% ± 0.01%. In EXPT2, seven mature light horses, four mares and three geldings (4.9 ± 4.4 years of age, mean ± SD; range, 2–14 years of age), were randomly assigned to one of two treatments (fasted [FST; n = 7] or fed [FD; n = 7]), followed by reversal of treatments 24 hours later. At 7:30 AM, FD horses were fed 2.1 kg DM grain-mix concentrate (187 IU vitamin E/kg DM) plus 3.3 kg DM mixed-grass hay, whereas FST horses received no feed. Neither group received any feed for 18 hours before 7:30 AM. Venous jugular blood samples were collected at 10:30 AM from all horses and analyzed for plasma TOC. The mean (±SD) within-horse paired-treatment difference was not significant (0.05 ± 0.12 μg/mL). The results suggest that variation in within-horse plasma TOC is relatively small over an 8-hour period in fasting horses and is unaffected 3 hours after a hay grain meal.  相似文献   

9.
Steady-state serum digoxin concentration ([digoxin]) was measured for 48 hours in 6 healthy cats after they were treated with digoxin tablets (0.01 mg/kg of body weight, q 48 h) for 10 days and again after concurrent treatment of identical duration with orally administered digoxin, aspirin (80 mg, q 48 h), furosemide (2 mg/kg, q 12 h), and a commercial low-salt diet. The concurrent treatment substantially altered digoxin pharmacokinetic properties, with a resultant increase in peak (mean +/- SEM; from 2.1 +/- 0.35 to 3.3 +/- 0.6 ng/ml), 8-hour (from 1.4 +/- 0.35 to 2.5 +/- 0.64 ng/ml), and 48-hour mean (from 1.1 +/- 0.22 to 2.2 +/- 0.57 ng/ml) serum [digoxin]; an increase in the number of hours during which serum [digoxin] was in the toxic range (from 3 +/- 1.7 to 24.7 +/- 9.8 h); and a decrease in oral clearance (from 0.15 +/- 0.04 to 0.08 +/- 0.02 L/h.kg). Of these differences, all but the 8-hour serum [digoxin] were significant at P less than 0.05. Similar sampling procedures were performed in 3 cats after administration of digoxin alone (0.01 mg/kg, q 48 h) until steady-state conditions were reached (10 days) and again after an additional 10 days of treatment. Differences were not noticed in digoxin pharmacokinetic properties. Eight-hour serum [digoxin] was shown to correlate closely with the mean serum [digoxin] at steady-state conditions when digoxin was administered every 48 hours. Variation in digoxin pharmacokinetic properties was noticed between cats.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

10.
OBJECTIVE: To evaluate the effects of twice-daily oral administration of a low-dose of trilostane treatment and assess the duration of effects after once-daily trilostane administration in dogs with naturally occurring hyperadrenocorticism (NOH). DESIGN: Prospective study. ANIMALS: 28 dogs with NOH. PROCEDURES: 22 dogs received 0.5 to 2.5 mg of trilostane/kg (0.23 to 1.14 mg/lb) orally every 12 hours initially. At intervals, dogs were reevaluated; owner assessment of treatment response was recorded. To assess drug effect duration, 16 of the 22 dogs and 6 additional dogs underwent 2 ACTH stimulation tests 3 to 4 hours and 8 to 9 hours after once-daily trilostane administration. RESULTS: After 1 to 2 weeks, mean trilostane dosage was 1.4 mg/kg (0.64 mg/lb) every 12 hours (n = 22 dogs; good response [resolution of signs], 8; poor response, 14). Four to 8 weeks later, mean dosage was 1.8 mg/kg (0.82 mg/lb) every 12 or 8 hours (n = 21 and 1 dogs, respectively; good response, 15; poor response, 5; 2 dogs were ill). Eight to 16 weeks after the second reevaluation, remaining dogs had good responses (mean dosages, 1.9 mg/kg [0.86 mg/lb], q 12 h [n = 13 dogs] and 1.3 mg/kg [0.59 mg/lb], q 8 h [3]). At 3 to 4 hours and 8 to 9 hours after once-daily dosing, mean post-ACTH stimulation serum cortisol concentrations were 2.60 and 8.09 Pg/dL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with NOH, administration of trilostane at low doses every 12 hours was effective, although 2 dogs became ill during treatment. Drug effects diminished within 8 to 9 hours. Because of potential adverse effects, lower doses should be evaluated.  相似文献   

11.
Fluconazole (100 mg) was administered to six adult cats as an intravenous infusion over 30 minutes, and the same cats received 100 mg of the drug orally 16 weeks later. The cats were bled repeatedly through an indwelling jugular catheter, the plasma fluconazole concentrations were assayed by high performance liquid chromatography, and the concentration-time data were subjected to a non-compartmental pharmacokinetic analysis. The mean (SD) intravenous half-life (13·8 [2·6] hours) was similar to that observed after oral dosing (12·4 [3·0] hours). The plasma clearances (intravenous 0·9 [0·1], oral 0·9 [0·2] ml min−1 kg−1) and the volumes of distribution at steady state (intravenous 1·1 [0·1], oral 1·0 [0·1] litre kg−1) were also similar after the two routes of dosing. The peak plasma concentration was reached 2·6 hours after oral dosing and the drug was completely bioavailable (1·09 [0·05]). On the basis of this single dose study, the administration of 50 mg fluconazole every eight hours to a 4 kg cat should produce average steady state plasma fluconazole concentrations of approximately 33 mg litre−1.  相似文献   

12.
ObjectiveTo describe the pharmacokinetics of pregabalin in normal dogs after a single oral dose.Study designProspective experiment.AnimalsSix adult Labrador/Greyhound dogs (four females and two males) aged 2.6 (2.6–5.6) years old (median and range) weighing 33.4 (26.8–42.1) kg.MethodsAfter jugular vein catheterization, the dogs received a single oral dose of pregabalin (～4 mg kg?1). Blood samples were collected at: 0 (before drug administration), 15 and 30 minutes and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 hours after drug administration. Plasma pregabalin concentration was measured by HPLC. Noncompartmental analysis was used to estimate pharmacokinetic variables.ResultsNo adverse effects were observed. The median (range) pharmacokinetic parameters were: Area under the curve from time 0 to 36 hours = 81.8 (56.5–92.1) μg hour mL?1; absorption half-life = 0.38 (0.25–1.11) hours; elimination half-life = 6.90 (6.21–7.40) hours; time over 2.8 μg mL?1 (the presumed minimal effective concentration) = 11.11 (6.97–14.47) hours; maximal plasma concentration (Cmax) = 7.15 (4.6–7.9) μg mL?1; time for Cmax to occur = 1.5 (1.0–4.0) hours. Assuming an 8-hour dosing interval, predicted minimal, average, and maximal steady state plasma concentrations were 6.5 (4.8–8.1), 8.8 (7.3–10.9), and 13.0 (8.8–15.2) μg mL?1. The corresponding values assuming a 12-hour interval were 3.8 (2.4–4.8), 6.8 (4.9–7.9), and 10.1 (6.6–11.6) μg mL?1.Conclusions and clinical relevancePregabalin 4 mg kg?1 PO produces plasma concentrations within the extrapolated therapeutic range from humans for sufficient time to suggest that a twice daily dosing regime would be adequate. Further study of the drug's safety and efficacy for the treatment of neuropathic pain and seizures in dogs is warranted.  相似文献   

13.
The pharmacokinetics, bioavailability, and distribution to the tears of ormetoprim (OMP; 5.5 mg/kg of body weight) and sulfadimethoxine (SDM; 27.5 mg/kg of body weight) were determined following IV or oral administration to 6 Holstein steers. After IV administration, the disposition kinetics of both drugs were best described by a 2-compartment open model. Sulfadimethoxine had a moderately rapid distribution phase, followed by a slower elimination phase, with a mean half-life (t 1/2) of 7.91 hours. The mean volume of distribution of SDM was 185 ml/kg, and the mean body clearance was 0.28 ml/min X kg. The concentration of SDM in tears was lower than the corresponding plasma concentration, and the elimination of SDM from tears (t 1/2 = 3.02 hours) was significantly faster than its elimination from plasma (t 1/2 = 7.91 hours). The disposition of OMP administered IV was characterized by a rapid distribution phase, followed by a rapid elimination phase (t 1/2 = 1.37 hours). The high values of the mean volume of distribution (1,450 ml/kg) and mean rate of body clearance (13.71 ml/min X kg) indicated that OMP was widely distributed in the body and was rapidly cleared from the body. Ormetoprim concentrations in tears exceeded corresponding plasma concentrations, and the elimination of OMP from tears was significantly slower (t 1/2 = 1.91 hours) than from plasma (t 1/2 = 1.37 hours). After oral administration of an OMP-SDM combination in bolus form, the absorption of SDM was slow (absorption t 1/2 = 3.32 hours), but complete.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

14.
Pharmacokinetic variables were calculated from time-concentration data obtained after IV (10 mg/kg of body weight; n =9) and oral (12.5 mg/kg to group A [n = 3]; 25 mg/kg to group B [n = 3]; and 50 mg/kg to group C [n = 3] pigs) cyclosporine (formerly, cyclosporine A) administration. Resulting mean (+/- SD) pharmacokinetic variables were as follows: half life of distribution, 0.96 (+/- 0.7) hours; half life of elimination, 7.71 (+/- 2.6) hours; volume of distribution at steady state, 4.47 (+/- 2.22) L/kg; volume of the central compartment, 1.71 (+/- 0.78) L/kg; and systemic clearance, 8.95 (+/- 2.7) ml/kg/min. Oral bioavailability was: overall 57 (+/- 19) %; group A, 44 (+/- 11) %; group B, 78 (+/- 15) %; group C, 48 (+/- 6) %. Time to peak concentration was 3.55 (+/- 0.88) hours. During the 22 days of daily oral cyclosporine administration, blood 24-hour trough concentrations were: group A, 224.3 (+/- 78.4) ng/ml; group B, 640.7 (+/- 174.6) ng/ml; and group C, 2,344 (+/- 1,095) ng/ml. Lymphoblast transformation stimulation index was suppressed in all pigs except 1, which had a corresponding cyclosporine concentration of 92.4 ng/ml. Minimal, although statistically significant, decreases in serum albumin and magnesium concentrations and increases in serum creatinine and urea nitrogen concentrations were evident in pigs of some treatment groups. Histologic examination of necropsy specimens revealed mild hepatic necrosis (n = 1 pig), renal tubular dilatation (n = 5), and pulmonary inflammation (n = 2). Pigs given 25 and 50 mg of cyclosporine/kg failed to gain weight.  相似文献   

15.
The pharmacokinetics of flunixin were studied in 6 adult lactating cattle after administration of single IV and IM doses at 1.1 mg/kg of body weight. A crossover design was used, with route of first administration in each cow determined randomly. Plasma and milk concentrations of total flunixin were determined by use of high-pressure liquid chromatography, using an assay with a lower limit of detection of 50 ng of flunixin/ml. The pharmacokinetics of flunixin were best described by a 2-compartment, open model. After IV administration, mean plasma flunixin concentrations rapidly decreased from initial concentrations of greater than 10 micrograms/ml to nondetectable concentrations at 12 hours after administration. The distribution phase was short (t1/2 alpha, harmonic mean = 0.16 hours) and the elimination phase was more prolonged (t1/2 beta, harmonic mean = 3.14 hours). Mean +/- SD clearance after IV administration was 2.51 +/- 0.96 ml/kg/min. After IM administration, the harmonic mean for the elimination phase (t1/2 beta) was prolonged at 5.20 hours. Bioavailability after IM dosing gave a mean +/- SD (n = 5) of 76.0 +/- 28.0%. Adult, lactating cows (n = 6) were challenge inoculated with endotoxin as a model of acute coliform mastitis. After multiple administration (total of 7 doses; first IV, remainder IM) of 1.1 mg/kg doses of flunixin at 8-hour intervals, plasma flunixin concentrations were approximately 1 microgram/ml at 2 hours after each dosing and 0.5 micrograms/ml just prior to each dosing. Flunixin was not detected in milk at any sampling during the study.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

16.
Fenprostalene, a prostaglandin F2 alpha analog, can be used to induce parturition in swine. As part of the approval process for that indication, pharmacokinetic characteristics of the absorption and elimination of fenprostalene and the depletion of drug residues from the principal edible tissues of swine were studied. Blood samples, urine, and feces were collected from 8 gilts (body weight, 95 +/- 1.7 kg) for up to 72 hours after a single dose of 0.5 mg of 13,14-[3H]-fenprostalene in polyethylene glycol-400 was administered SC. At intervals of 24, 48, 72, and 168 hours after dosing, 2 gilts each were killed, and samples of liver, kidney, muscle, and abdominal fat were obtained for analysis. The mean (+/- SEM) maximal concentration of fenprostalene radioequivalents in plasma (0.41 +/- 0.05 nanogram-equivalents/ml; n = 8) was observed at 12 hours and decreased biexponentially, with half-lives of approximately 8 hours and 9 days. Mean cumulative recovery (n = 4) of the administered dose by 72 hours was 61.2 +/- 5.9% in urine and 18.5 +/- 2.6% in feces. The highest tissue fenprostalene concentration was in kidneys and liver, probably reflecting the role of those organs in excreting fenprostalene. Rates of depletion of fenprostalene equivalents from the injection site, kidneys, and liver were comparable with those previously observed in cattle. The composition of residue in the liver of 2 gilts slaughtered 12 hours after SC administration of [3H]-fenprostalene was examined in a second study. Results suggested that approximately 4% of the total residue was pharmacologically potent fenprostalene or the carboxylic acid form of fenprostalene.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

17.
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18.
Summary

An intravenous low dosage of sulphanilamide (SAA) (14.0 mg/kg) to 6 pre‐ruminant calves revealed a biphasic SAA plasma disposition with a mean elimination half‐life of 4.1 h. The main metabolite in plasma was N4‐acetylsulphanilamide (N4), which 4 hours after injection exceeded the parent SAA plasma concentration. Urinary recovery of SAA was 10 to 16% of the dose; of N4, it was at least 69%. Traces of the N1‐acetyl (N1) metabolite and the doubly acetylated derivative (N1N4) were present in urine. The renal clearances of the N1 and N4 metabolites showed a tubular secretion pattern, which was at least 2 to 6 times higher than that of SAA.

A single high oral SAA dose of 200 mg/kg to 3 dairy cows resulted in extensive metabolism of SAA into N4 N1, and N1N4 metabolites; their mean maximum plasma concentrations were 64, 48, 0.72 and 24 μg/ml, respectively. The mean disposition half‐life of SAA in plasma and milk was 10 h. In milk the metabolite concentrations exceeded those in plasma; the N4 and N1N4 metabolite concentrations in milk exceeded that of SAA. The mean maximum concentrations of SAA, N4, N1, and N1N4 in milk were 52, 89, 2.3, and 98 pg/ml. respectively. For SAA and its metabolites, the binding to plasma and milk proteins was determined. No glucuronide or sulphate conjugates of SAA and its acetyl metabolites could be found in plasma, milk, or urine.

Based on the sensitivity of the bioassay (0.2 μg SAA/ml), a withholding time of 5 days was suggested for milk following single oral SAA dosage of 200 mg/kg.  相似文献   

19.
Huang, R. A., Letendre, L. T., Banav, N., Fischer, J., Somerville, B. Pharmacokinetics of gamithromycin in cattle with comparison of plasma and lung tissue concentrations and plasma antibacterial activity. J. vet. Pharmacol. Therap. 33 , 227–237. The pharmacokinetics (PK) and dose proportionality of gamithromycin (ZACTRAN®), a novel azalide, after a single intravenous (i.v.) dose of 3 mg/kg or subcutaneous (s.c.) injection at 3, 6 and 9 mg/kg body weight were studied in 13 male castrate and 13 female Angus cattle. Following i.v. administration, the mean area under the curve extrapolated to infinity (AUCinf) was 4.28 ± 0.536 μg·h/mL, and mean elimination half‐life (t1/2) was 44.9 ± 4.67 h, with a large volume of distribution (Vss) of 24.9 ± 2.99 L/kg and a high clearance rate (Clobs) of 712 ± 95.7 mL/h/kg. For cattle treated with s.c. injection of 3, 6 or 9 mg/kg, mean AUCinf values were 4.55 ± 0.690, 9.42 ± 1.11 and 12.2 ± 1.13 μg·h/mL, respectively, and the mean elimination half‐lives (t1/2) were 51.2 ± 6.10, 50.8 ± 3.80 and 58.5 ± 5.50 h. Gamithromycin was well absorbed and fully bioavailable (97.6–112%) after s.c. administration. No statistically significant (α = 0.05) gender differences in the AUCInf or elimination half‐life values were observed. Dose proportionality was established based on AUCInf over the range of 0.5 to 1.5 times of the recommended dosage of 6 mg/kg of body weight. Further investigations were conducted to assess plasma PK, lung/plasma concentration ratios and plasma antibacterial activity using 36 cattle. The average maximum gamithromycin concentration measured in whole lung homogenate was 18 500 ng/g at first sampling time of 1 day (～24 h) after treatment. The ratios of lung to plasma concentration were 265, 410, 329 and 247 at 1, 5, 10 and 15 days postdose. The lung AUCinf was 194 times higher than the corresponding plasma AUCinf. The apparent elimination half‐life for gamithromycin in lung was 90.4 h (～4 days). Antibacterial activity was observed with plasma collected at 6 h postdose with a corresponding average gamithromycin plasma concentration of 261 ng/mL. In vitro plasma protein binding in bovine plasma was determined to be 26.0 ± 0.60% bound over a range of 0.1–3.0 μg/mL of gamithromycin. The dose proportionality of AUC, high bioavailability, rapid and extensive distribution to lung tissue and low level of plasma protein binding are beneficial PK parameters for an antimicrobial drug used for the treatment and prevention of bovine respiratory disease.  相似文献   

20.
OBJECTIVE: To determine pharmacokinetic variables and pharmacologic effects of the S(-) isomer of bupivacaine (S[-]-BPV) in dogs. ANIMALS: 6 adult male Beagles. PROCEDURE: Dogs received S(-)-BPV (1 mg/kg of body weight) i.v., and 15 days later, the same dogs received 1.8 mg/kg epidurally. Pharmacokinetic variables and pharmacologic effects were determined for each route of administration. RESULTS: After i.v. administration, plasma concentration versus time curves were adjusted, using biexponential equations that indicated a rapid distribution phase followed by a slower elimination phase, with a mean +/- SD half-life of 33.5 +/- 17.0 minutes. Mean plasma clearance was 21.0 +/- 10.7 ml/min/kg, and mean volume of distribution at steady state was 0.8 +/- 0.2 L/kg. After i.v. administration, mean peak plasma concentration was 2.6 +/- 0.7 micrograms/ml; after epidural administration, it was 0.9 +/- 0.5 microgram/ml at approximately 3 minutes. Half-life after epidural administration was 5 times longer than that observed after i.v. administration. Motor block began immediately after the end of epidural administration and lasted for 3 to 4 hours. Changes in systolic blood pressure and heart rate after epidural administration were slight but occurred at the same time that plasma concentration peaked. After i.v. administration, motor block or variations in physiologic variables studied were not observed. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, the pharmacologic behavior of S(-)-BPV was similar to that of the bupivacaine racemate, but motor block attributable to S(-)-BPV lasted longer than that attributable to the racemate, with lower plasma concentrations observed at equivalent sample collection times.  相似文献   

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