ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00616.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The pharmacokinetics of gentamicin was investigated in six newborn male piglets, aged from 4 to 12 h at the time of administration of the drug, and six 42‐day‐old castrated male piglets, that had been weaned for 2 weeks following a single intravenous bolus of 5 mg/kg. Gentamicin was measured in serum and in urine by a fluorescence polarization immunoassay. The serum concentrationtime data were best described by a three‐compartment open model. A rapid initial distribution phase (± phase) was observed in every animal. The serum β half‐life (t1/2β) was significantly longer in the newborn piglets (mean ± SEM) (5.19 ± 0.30 h) than in the older group (3.50 ± 0.23 h) (P<0.05). Mean residence time was similarly longer in younger piglets (6.62 ± 0.57 h) than in older animals (2.86 ± 0.11 h) (P<0.05). The steady‐state volume of distribution (Villswas significantly larger for younger pigs (0.785 ± 0.036 L/kg) than in elder pigs (0.474 ± 0.029 L/kg) (P<0.05). Urinary γ half‐life (t1/27u) was 72.66 ± 10.78 h in the newborn piglets and 69.20 ± 14.77 h in the 42‐day‐old animals. A urinary δ phase was observed in three of the 42‐day‐old piglets and gave a mean (t1/2δuof 232.01 ± 14.55 h. Percentages of urinary recovery of the administered dose after 144 h were 94.18 ± 1.01 and 94.04 ± 1.12 in the newborn and 42‐day‐old animals, respectively. Serum gentamicin clearance was significantly lower in younger animals (0.121 ± 0.007 L/h±kg) than in the 42‐day‐old group (0.166 ± 0.010 L/h·kg). It is suggested that in the newborn piglets, the increase ofVd(ss)could be explained by a higher proportion of extracellular water while the lower clearance could be attributed to a reduced glomerular filtration capacity. Gentamicin dosage requirement in the newborn piglets would therefore have to be adjusted, in order to take into consideration the observed differences in the mean

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00617.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Pharmacokinetics of florfenicol 30% injectable solution was determined in lactating cows after intravenous, intramammary and intramuscular administration. Serum concentration‐time data generated in the present study were analysed by non‐compartmental methods based on statistical moment theory. Florfenicol half‐life was 176 min, mean residence time 129 min, volume of distribution at steady‐state 0.35 L/kg, and total body clearance 2.7 mL/min·kg after intravenous administration at 20 mg/kg. The absorption after intramuscular administration appeared slow and the kinetic parameters and the serum concentration vs. time curve were characteristic of absorption rate‐dependent elimination. The absorption after intramammary administration of florfenicol at 20 mg/kg was good (53.9%) and resulted in serum concentrations with apparent clinical significance. The intramammary administration resulted in serum florfenicol concentrations that were significantly higher than the respective serum concentrations following Intravenous administration 4 h after administration and thereafter. Florfenicol absorption was faster from the mammary gland than from the muscle. The maximum serum concentrations (Cmax) were 6.9 μg/mL at 360 min after intramammary administration and 2.3 μg/mL at 180 min after intramuscular administration. The bioavailability of florfenicol was 54% and 38% after intramammary and intramuscular administration, respectively. TheCmaxin milk was 5.4 μg/mL at 180 min after intravenous and 1.6 μg/mL at 600 min after intramuscular

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00618.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Glomerula filtration rate (GFR), plasma creatinine concentration (CR), and plasma urea nitrogen concentration (BUN) were measured in 129 adult dogs with reduced renal mass. A preliminary examination of the relationship between CR and GFR was conducted, and the inverse model (GFR vs. 1/CR) was chosen for further evaluation. The slope of the regression of GFR on 1/CR which was computed from actual data was not statistically different from a theoretical regression line generated from the clearance equation.Evaluation of subsets of the population revealed no significant difference between male (n= 69) and female (n = 60) dogs on the slope of the regression equations. Diets differing in protein concentration (16% protein, n = 35: 21% protein, n = 75: 32% protein,n= 19) did not cause a significant difference in the slope of the regression equations.The regression equation and the confidence intervals generated in this study may be used to predict a probable range of GFR values from CR in individual dogs. Such values may be useful in adjusting drug dosages in dogs with renal disease. However, since the derived equation did not differ significantly from the theoretical inverse relationship between GFR and CR, it remains to be established whether the equation is advantageous.

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00619.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The potency of selected antibacterials on mastitis‐causingEscherichta coli, Streptococcus agalactiaeandStreptococcus uberisin milk, whey and Iso‐sensitest broth (ISB) was compared, based on the suppression of bacterial β‐glucuronidase production. The β‐glucuronidase activity in the samples was analysed by substrate‐defined fluorometry where the turbidity of milk does not disturb the assay. In ISB, all fourE. colistrains were susceptible to enrofloxacin and gentamicin, sulfadoxintrimethoprim and tetracycline.S. agalactiaeandS. uberisstrains were susceptible in ISB to most of the antibacterials tested. The antibacterial potency of sulfadoxintrimethoprim, tetracycline, novobiocin, gentamicin and enrofloxacin on E.coliandS. agalactiaewere considerably decreased in milk as compared with that in ISB. However,S. uberisseemed to be more susceptible to antibacterials in milk or whey than in ISB. Regression analysis of the sigmoidal dose‐response curves of sulfadoxin‐trimethoprim showed that slopes of the linearized lines seemed to become less steep in milk than in the artificial broth medium, indicating a shift of the bactericidic effect in ISB towards a bacteriostatic

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00620.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The dose‐related effects of phenylbutazone and Depo‐Medrol® on chondrocyte viability and chondrocyte‐mediated synthesis and depletion of proteoglycans were investigated using cultured explants of equine middle carpal joint articular cartilage. Explants from 12 horses (941 × 3 mm diameter) were cultured for a total of 5 days, which included 3 days' exposure to either phenylbutazone (0, 2, 20, 200 or 2000 μg/mL) or Depo‐Medrol (0, 20, 200 or 2000 μg/mL). For each explant, amino sugar content was used as a measure of proteoglycan content,35S incorporation as a measure of the rate of proteoglycan synthesis and the number of pyknotic nuclei as a measure of cell death. During culture, control explants remained metabolically active and viable but suffered a net loss of proteoglycans. Proteoglycan loss was reduced by the presence of either phenylbutazone or Depo‐Medrol. This effect was significant at clinically relevant concentrations of phenylbutazone (2–20 μg/mL), but not Depo‐Medrol (20–200 μg/mL). Depo‐Medrol caused a dose‐dependent suppression of proteoglycan synthesis at all concentrations, but chondrocyte viability was affected only at the 2000 μg/mL dose. Phenylbutazone affected proteoglycan synthesis and cell viability only at the 2000 μg/mL concentration. At all concentrations, the anticatabolic effects of each drug influenced the proteoglycan content of the explants far more than did any antianabolic or cytotoxic drug effect. The results suggest that the therapeutic potential of both phenylbutazone and Depo‐Medrol may not be restricted to their anti‐inflammatory effects o

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00621.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

α2‐adrenoceptor agonist drugs can cause respiratory changes leading to a short period of hypoxaemia in sheep. It has been suggested that this is due to transient platelet aggregation and pulmonary microembolism. If platelet aggregation were to follow platelet activation in response to the administration of α2agonists, plasma thromboxane levels would be expected to rise. This study was carried out to measure plasma thromboxane B2concentrations before and after the intravenous administration of the α2‐agonist drug xylazine at a dose of 0.1 mg/kg. It was found that the plasma thromboxane concentration rose by 320% and, furthermore, the rise was prevented by the prior administration of atipamezole hydrochloride (0.125 mg/kg), an α2‐adrenoceptor a

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00622.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The elimination kinetics and the formation of the monoethylglycinexylidide (MEGX), a major metabolite of lidocaine, were studied in camels deprived of water for 14 days. The study was conducted on four camels in a crossover design. Lidocaine was administered intravenously at a dose of 1 mg/kg to adult female camels when water was givenad libitum(stage 1) and to the same camels after 14 days of dehydration. Blood samples were taken up to 6 h after dosing. Serum lidocaine and MEGX levels were analysed by polarization fluorescence immunoassay. The elimination profiles of lidocaine and the formation of the metabolite MEGX in the two phases of the study were essentially identical. No difference in any pharmacokinetic parameter was noticed between normally hydrated and water‐deprived camels. It is thus concluded that dehydration does not affect the cytochrome P450 isozymes involved in degradation of lidocaine to MEGX nor does it affect the hepatic blood flow, which is a major determinant in the clearance of lidocaine. The very low clearance of lidocaine in the camel in comparison with other ruminant or monogastric mammals may be associated with the camel's ability to survive drought in the deser

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00623.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The bioavailability of S(+) and R(‐) ketoprofen (KTP) in six horses was investigated after oral administration of the racemic (rac) mixture. Two oral formulations were studied, an oil‐based paste containing micronised rac‐KTP and powder from the same source in hard gelatin capsules, each at a dose rate of 2.2 mg/kg. For the oil‐based paste two feeding schedules were used; horses were either allowed free access to food or access to food was restricted for 4 h before and 5 h after dosing. The drug in hard gelatin capsules was administered to horses with restricted access to food. After intravenous administration of rac‐KTP, S(+) enantiomer concentrations exceeded those of the R(‐) enantiomer. For S(+) and R(‐)KTP. respectively, pharmacokinetic parameters were,t1/2β0.99 ± 0.14 h, 0.70 ±0.13 h;C/B0.56±0.09,0.92±0.20 L/h/kg; Vd(ss), 0.53 ±0.11.0, 61±0.10L/kg. Following oral administration of rac‐KTP as the oil‐based paste to horses with free access to food, there were no detectable concentrations in plasma in three animals at any sampling time, while a fourth animal showed very low concentrations at two sampling times only. In the two remaining horses very low but detectable concentrations were present for 5 h. In the horses with restricted access to food, rac‐KTP paste administration produced higher concentrations in plasma. However, bioavailability was very low, 2.67 ± 0.43 and 5.75 ± 1.48% for R(‐) and S(+)KTP, respectively. When administered as pure drug substance in hard gelatin capsules, absorption of KTP was fairly rapid, but incomplete. Bioavailability was 50.55 ± 10.95 and 54.17 ±9.9% for R(‐) and S(+)KTP, respectively.This study demonstrates that rac‐KTP had a modest bioavailability when administered as a micronised powder in hard gelatin capsules to horses with restricted access to food. When powder from the same source was administered as an oil‐based paste, it was for practical purposes not bioavailab

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00624.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The pharmacokinetics of oral and intravenous allopurinol was studied in five horses and compared with intravenous oxypurinol. The plasma concentration vs. time curves, following intravenous administration of 5 mg/kg, were best described by the biexponential equations Cp = 106.58e‐25.141+ 159.93e‐10.96tfor allopurinol and Cp = 321.09e‐972t+ 82.39e‐0.44tfor oxypurinol. Allopurinol was rapidly removed from the plasma, compared to oxypurinol, with an elimination half‐life (t1/2β) of 0.09 h and an area under the curve (AUC) of 19.8 μmol·h/L after intravenous administration, while thet1/2βandAUCof oxypurinol were 1.09 h and 231 μmol·h/L, respectively. The bioavailability of allopurinol was low (14.3%), although no allopurinol was detected in the plasma of two horses after oral administration. However, theAUCof drug and metabolite after intravenous administration of allopurinol was equivalent to that of intravenously injected oxypurinol. The results suggest that allopurinol is rapidly metabolisedin vivoand that the majority of the pharmacological activity of allopurinol in the horse may result from the action of the active metabol

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00625.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY