摘要:

The pharmacokinetics of ampicillin and amoxicillin following intravenous administration at a dose rate of 15 and 10 rng/kg respectively were studied in four healthy adult horses. Pharmacokinetics of pivampicillin and amoxicillin were studied after oral administration to four healthy adult horses. Pivampicillin, a prodrug of ampicillin, was administered orally to starved and fed horses at a dose rate of 19.9 mg/kg, which is equivalent on a molecular basis to 15 mg/kg ampicillin. Amoxicillin was administered orally to starved horses only, at a dose rate of 20 mgkg. Ampicillin and amoxicillin concentrations in plasma, synovial fluid and urine were determined. Mean biological half‐life of intravenously administered ampicillin and amoxicillin was 1.72 and 1.43 h respectively, whilst the distribution volume (Vss) appeared to be 0.180 and 0.192 l/kg. Orally administered pivampicillin' and amoxicillin were rapidly absorhed. A maximum concentration in plasma of 3.80 μg/ml was reached. 2 h after administration of pivampicillin to starved horses; in fed horses a maximum concentration of 5.12 μg/ml was reached 1 h after administration. After oral administration of amoxicillin a maximum concentration of 2.03 μg/ml was reached after 1 h. The (absolute) bioavailability of pivampicillin administered orally was 30.9% in starved horses and 35.9% in fed horses. The bioavailability of amoxicillin administered orally was 5.3% in starved ho

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1992.tb01010.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The correlation between pharmacokinetics and dynamics of furosemide was investigated in anaesthetized dogs. After intravenous administration (i.v.) of furosemide (5 mg/kg), the plasma concentration declined rapidly with biexpo‐nential decay. The half‐life (t1/2β) of the late phase of elimination was 0.931 ± 0.187 h and the apparent volume of distribution at steady state was 0.25 ± 0.043 1/Kg. The total clearance (ClIOL) was 0.435 ± 0.031 1/h/kg, in which the renal clearance was 0.260 ± 0.020 (about 60% ofCltOt). The change in rate of urinary excretion of furosemide was similar to the plasma concentration decay curve. The diuretic effect of furosemide was accompanied by an extreme increase in the excretion rate of sodium and chloride, but not potassium. The relationships between;he diuretic response and the plasma concentration or the urinary excretion rate of furosemide was depicted by sigmoidal dose‐response curves in both cases. The half‐maximum effect was obtained at 1.5 μg/ml of plasma concentration or at 80 μg/min of excretion rate

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1992.tb01011.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Seven mature thoroughbred horses, weighing between 400 and 541 kg, were each injected intra‐articularly into three joints with 6 mg/joint of triamcinolone acetonide (Vetalog). The fourth joint, the control, was injected with saline. Synovial fluid was taken from all four legs of the horses on days 1, 2, 3, 4, 5, 6, 7, 8, 11, and 15 following the injections. Triamcinolone acetonide was assayed by a radioimmunoassay. Blood was collected at 1, 2, 4, 6, 12 h and on days 1, 2, 3, 4, 5, 6, 7, 8, 11, and 15 following injection of either triamcinolone or saline. Both cortisol and triamcinolone were assayed. The results show that the synovial fluid level of triamcinolone was 7.5 μg/ml 1 day following treatment and decreased to 10 ng/ml by the 4th day. These low levels were maintained for approximately 14 days. By the 15th day, the triamcinolone was below a detectable level. Serum levels of triamcinolone increased to 3 ng/ml within 1 h and further increased to a peak of 4.3 ng/ml at 4th h. The level then decreased to 2 ng/ml at 24 h and to nearly an undetectable level in 48 h. The mean level of serum cortisol, on the other hand, gradually decreased as the serum level of triamcinolone increased. As the serum level of triamcinolone reached an undetectable level on the 2nd day, the serum cortisol level gradually increased and returned to the pre‐administration level by the 5th day. These results showed that the intra‐articular administration of triarncinolone maintained triamcinolone in the synovial fluid for 4–14 days and that the triamcinolone reached the blood within 1 h. The serum level of triamcinolone was maintained for 2 days and resulted in the inhibition of adrenal function fo

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1992.tb01012.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Phenothiazine and thiabendazole were studied for their ability to antagonize venoconstriction induced by ergonovine, and the biogenic amine serotonin, in the isolated dorsal pedal vein of cattle. The two compounds are commercially available, approved for usage in cattle and have been reported to reverse some of the toxic effects associated with the intake ofAcremonium coenophialum‐infested fescue forage by cattle. Neither compound had any antagonistic activity against venoconstriction induced by ergonovine. However, thiabendazole did have some activity against venoconstriction induced by serotonin. Ergot alkaloids are known to cause venoconstriction through effects on biogenic amine receptors, including serotonergic receptors, and since thiabendazole has anti‐serotonin activity, part of the reported beneficial effects of thiabendazole in alleviating fescue toxicity may be due to the anti‐serotonin activity of the drug. Further work is needed to determine if phenothiazine and thiabendazole have any effect on other types of alkaloids that are present inA. coenophialum‐infested

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1992.tb01013.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The pharmacokinetics of intravenous (i.v.) and intramuscular (i.m.) single‐dose administration of acyclovir were determined in Quaker parakeets. After i.v. injection at a dose of 20 mg/kg of acyclovir, elimination half‐life was estimated at 0.65 h, volume of distribution at steady state was 627.65 ml/kg, and clearance was 11.22 ml/kg/min. The estimated pharmacokinetic values after i.m. injection at a dose of 40 mg/kg of acyclovir were an elimination half‐life of 0.71 h and a bioavailability of 90.1%. The peak plasma acyclovir concentration occurred at 15 min when the drug was administered i.m. Plasma concentrations of acyclovir were undetectable 4–6 h after i.v. administration and 68 h after i.m. administration. Oral (capsules) and intravenous (sodium salt) formulations of acyclovir were given by gavage at 80 mg/kg. Peak concentrations with the sodium salt formulation were lower and developed more slowly than with the capsules. In studies designed to detect excessive drug accumulation or adverse side effects, acyclovir was administered i.m. at 40 mg/kg every 8 h for 7 days. Plasma concentrations were determined 15 min after (peak) and just prior to drug administration (trough). In another study acyclovir was gavaged at a dose of 80 mg/kg every 8 h for 4 days. Acyclovir plasma concentrations were determined just prior to and 2 h after drug administration. In both experiments, the birds maintained normal appetite and weight and did not exhibit excessive drug accumulation. Acyclovir plasma concentrations ranging from 2.07 ± 1.09 μg/ml to 3.93 ± 1.13 μg/ml were maintained for 4 days when acyclovir was administered in the feed and water (sole source of food and water). The feed contained 400 mg of acyclovir in 2 quarts of parrot seed and the water contained 1 mg of acyclovir per

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1992.tb01014.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Quantitative EEG was assessed in six dogs anaesthetized with 1.8% end‐tidal isoflurane concentration and following diazepam (0.2 mg/kg i.v.) administration. Ventilation was controlled to maintain pormocapnia. Five dogs were subsequently given the benzodiazepine antagonist, flumazenil (0.04 mg/kg i.v.), and quantitative EEG was recorded. One dog received a saline injection following diazepam (as a control) and quantitative EEG was recorded for an additional 2.5 h. Heart rate, arterial blood pressure, esophageal temperature, arterial pH and blood gas tensions, end‐tidal CO2tension and end‐tidal isoflurane concentration were monitored throughout the study. A 21 lead linked‐ear montage was used for recording EEG. Quantitative EEG data were stored on an optical disc for analysis at a later date. Values for absolute power of EEG were determined for θ, δ, α, and β frequencies. Cardiovascular parameters remained stable throughout the study. Diazepam administration was associated with decreased absolute power in all frequencies of EEG at all electrode sites. The duration of diazepam‐induced decreased absolute power of EEG was at least 3 h in one dog. Administration of flumazenil antagonized diazepam‐induced decreased absolute power of EEG in all frequencies at all electrode sites. We conclude that quantitative EEG provides a relatively non‐invasive, objective measure of diazepam‐ and flumazenil‐induced changes in cortical activity during i

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1992.tb01015.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The effects of modulation of liver microsomal sulphoxidation on the disposition kinetics of netobimin (NTB) metabolites were investigated in sheep. A zwitterion suspension of NTB was given orally at 7.5 mg/kg to sheep either alone (control treatment) or co‐administered with methimazole (MTZ) orally (NTB + MTZ oral treatment) or intra‐muscularly (NTB + MTZ i.m.) at 3 mg/kg. Blood samples were taken serially over a 72 h period and plasma was analysed by HPLC for NTB and its major metabolites, i.e. albendazole (ABZ), albendazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO2). Only trace amounts of NTB parent drug and ABZ were detected in the earliest samples after either treatment. There were significant modifications to the disposition kinetics of ABZSO in the presence of MTZ. ABZSO elimination half‐life increased from 7.27 h (control treatment) to 14.57 h (NTB + MTZ oral) and to 11.39 h (NTB + MTZ im.). ABZSOAUCswere significantly higher (P<0.05) for the NTB + MTZ oral treatment (+55%) and for the NTB + MTZ i.m. treatment (+61%), compared with the NTB alone treatment. The mean residence times for ABZSO were 12.66 5 0.68 h (control treatment), 18.85 ± 2.35 h (NTB + MTZ oral) and 17.02 ± 0.90 h (NTB + MTZ im.). There were no major changes in the overall pharmacokinetics of ABZSO2for the concomitant MTZ treatments. However, delayed appearance of this metabolite in the plasma resulted in longer ABZSO2lag times and a delayed Tmaxfor treatments with MTZ. We have demonstrated that co‐administration of MTZ, both orally and intra‐muscularly, results in an altered pharmacokinetic pattern for the metabolites of NTB. The changed pharmacokinetic profile of the anthelmintically‐active ABZSO metabolite may result in enha

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1992.tb01016.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Photodynamic therapy is a promising new treatment for local eradication of cancer. Little work has been done to define the pharmacokinetics of photodynamic drugs or the variability in drug disposition that may occur between different species and pathophysiological states of tissues. Pharmacokinetic studies of tin‐etiopurpurin (SnET2), a lipophilic photosensitizer, were conducted on six Beagle dogs and six Sprague‐Dawley rats. Blood was collected up to 24 h following drug administration for measurement of tin‐etiopurpurin concentration. Dogs and rats were euthanatized 24 h post‐administration and tissues were collected for drug analyses. The plasma drug concentrations were best described by a 2‐comparment model (Ct = Ae‐αt+ Be‐βt). Median distribution and elimination half‐lives were 0.24 and 0.34 h and 10.21 and 5.25 h for dogs and rats, respectively. The apparent volumes of distribution were 4.26 ± 1.75 L/kg for dogs and 1.84 ± 0.36 L/kg for rats. Systemic clearance was 7.56 ± 2.45 ml/kg/min and 6.63 ± 0.91 ml/kg/min for dogs and rats, respectively. Drug was detected in all tissues analyzed 24 h after drug administration. Drug was detected only sporadically in skin and muscle and was generally below the limit of detection of the assay. Where comparisons could be made, concentrations of SnET2 were significantly greater in all tissues except jejunum of rats compared to dogs 24 h afte

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1992.tb01017.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Clorsulon was measured in plasma and urine of sheep and goats after administration of a single intravenous (i.v.) and after a single oral dose of 7 mg/ kg. A three‐compartment model with elimination occurring from the central compartment was determined to best describe the i.v. data, whereas a one‐compartment model with a single exponential absorption phase best described the oral plasma data. The bioavailability of orally administered clorsulon was approximately 55% in goats and 60% in sheep. Peak plasma concentrations occurred at 14 h and 15 h after oral administration in goats and sheep, respectively. Absorption from the gastro‐intestinal tract effectively prolonged the elimination of clorsulon by increasing the elimination half‐life from 17 to 28 h in sheep and from 12 to 23 h in goats for the i.v. and oral routes, respectively. In both goats and sheep, approximately 50% of the i.v. dose was recovered in urine as parent drug at 48 h after administration, whereas 41 % and 30% of the dose was recovered after oral administration for goats and sheep, respectively. The elimination rate constant (kel) in goats was nearly twice as large as the value determined in sheep, and the area under the i.v. plasma curve in goats was only 63% of the value in sheep indicating that goats are more effective in their capacity to eliminate clorsulon than are sheep. These differences in drug disposition between sheep and goats may account for the reduced efficacy of clorsulon reported i

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1992.tb01018.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The effects of the intravenous (i.v.) administration of 1.1 mg/kg of flunixin meglumine on thromboxane B2(TxB2) concentrations were studied in sedentary and 2‐year‐old horses in training. The baseline TxB2serum concentrations generated during clotting were 2.89 ± 81, 2.19 ± 0.25 and 0.88 ± 0.12 ng/ml for the 2‐year‐old Thoroughbreds in training, sedentary horses under 10 and over 10 years old, respectively. There was a significant difference in baseline TxB2concentrations between older and younger horses (P<0.005). Significant reduction in TxB2production from baseline were noted at 1 (P<0.01) and 4 h (P<0.01) but not at 8 h after flunixin administration. The percent reduction in serum TxB2concentration at 1 h after the administration of flunixin was 68.6 ± 7.8 and 45.2 ± 6.8 for the training and sedentary horses, respectively; the differences were significant (P<0.04). Serum concentrations of TxB2returned to baseline values by 12–16 h after flunixin administration. The results of this study indicate a difference in the TxB2concentrations of older vs. younger horses and a difference in the suppression of TxB2after the administration of flunixin in 2‐year‐old Thoroughbreds in training compared to sedentary horses. The results of this study suggest that the detection of low concentrations of flunixin in urine 24 h post‐administration may not represent pharmacologic effective concentrations o

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1992.tb01019.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY