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1.
As certain quinolones can interfere with the metabolism of theophylline by competitive inhibition of the hepatic microsomal cytochrome P450 system, concomitant use of these drugs with theophylline could result in theophylline toxicity. This study investigated the effect of orally administered marbofloxacin (2 and 5 mg/kg each once daily) on steady-state plasma pharmacokinetics of theophylline after concomitant oral administration of a sustained release theophylline preparation in dogs. Marbofloxacin caused some alteration in theophylline metabolism. A 2 mg/kg dose of marbofloxacin did not clearly result in an increased area under the concentration--time curve (AUC) or decreased clearance of theophylline, but at a dose of 5 mg/kg, a statistically significant increase in AUC and a decrease in the total clearance of theophylline was found. The 26% reduction in theophylline clearance is probably not clinically significant in healthy dogs, but for dogs with renal impairment, there might be a chance of theophylline accumulation when dosed concomitantly with marbofloxacin.  相似文献   

2.
Background: Hypothyroidism affects renal function in a manner opposite the effects of hyperthyroidism.
Objective: To evaluate the effects of experimentally induced hypothyroidism on glomerular filtration rate (GFR) and basal plasma creatinine concentration in dogs.
Animals: Sixteen anestrous, female dogs.
Methods: Hypothyroidism was induced by administration of 131I in 8 dogs, and 8 healthy euthyroid dogs acted as controls. Exogenous plasma creatinine clearance (an estimate of GFR) was measured in all dogs before (control period) and 43–50 weeks after induction of hypothyroidism (posttreatment period). Other pharmacokinetic parameters of creatinine were also determined.
Results: No significant difference was observed for basal plasma creatinine concentration and creatinine clearance between control and hypothyroid dogs in the control period. In the posttreatment period, mean ± SD creatinine clearance in the hypothyroid group (2.13 ± 0.48 mL/min/kg) was lower ( P < .001) than that of the control group (3.20 ± 0.42 mL/kg/min). Nevertheless, basal plasma creatinine concentrations were not significantly different between the hypothyroid and control groups (0.74 ± 0.18 versus 0.70 ± 0.08 mg/dL, respectively) because endogenous production of creatinine was decreased in hypothyroid dogs (22 ± 3 versus 32 ± 5 mg/kg/d, P =.001).
Conclusion and Clinical Importance: Hypothyroidism causes a substantial decrease in GFR without altering plasma creatinine concentrations, indicating that GFR evaluation is needed to identify renal dysfunction in such patients.  相似文献   

3.
Background: Glomerular filtration rate (GFR) is decreased in humans with hypothyroidism, but information about kidney function in dogs with hypothyroidism is lacking.
Hypothesis: Hypothyroidism influences GFR in dogs. The objective of this study was to assess GFR in hypothyroid dogs before implementation of thyroxine supplementation and after re-establishing euthyroidism.
Animals: Fourteen hypothyroid dogs without abnormalities on renal ultrasound examination or urinalysis.
Methods: Blood pressure and GFR (measured by exogenous creatinine clearance) were measured before treatment (T0, n = 14) and at 1 month (T1, n = 14) and at 6 months (T6, n = 11) after beginning levothyroxine supplementation therapy (20 μg/kg/d, PO). The response to therapy was monitored at T1 by measuring serum total thyroxine and thyroid stimulating hormone concentrations. If needed, levothyroxine dosage was adjusted and reassessed after 1 month. Statistical analysis was performed using a general linear model. Results are expressed as mean ± standard deviation.
Results: At T0, the average age of dogs in the study group was 6.3 ± 1.4 years. Their average body weight decreased from 35 ± 18 kg at T0 to 27 ± 14 kg at T6 ( P < .05). All dogs remained normotensive throughout the study. GFR increased significantly with levothyroxine supplementation; the corresponding results were 1.6 ± 0.4 mL/min/kg at T0, 2.1 ± 0.4 at T1, and 2.0 ± 0.4 at T6 ( P < .01).
Conclusion: GFR was <2 mL/min/kg in untreated hypothyroid dogs. Re-establishment of a euthyroid state increased GFR significantly.  相似文献   

4.
This study evaluated the pharmacokinetics, the sedative and anti-nociceptive effects of intravenous hydromorphone in dogs. Five adult dogs were administered hydromorphone (0.1 mg/kg and 0.2 mg/kg) and morphine (0.5 mg/kg and 1 mg/kg) at weekly intervals. Blood samples were drawn before and at 1, 2, 5, 15, 30, 60 and 120 min after drug administration. Plasma hydromorphone only was measured by high pressure liquid chromatography (HPLC) with electrochemical detection and pharmacokinetic parameters calculated. Anti-nociceptive and sedation scores were submitted to Kruskal-Wallis one-way anova on ranks and post-hoc Bonferroni test with 5% significance level. The data fitted a two-compartment model with a fast distribution (<1 min for both doses) and slower elimination rate. Mean elimination half-life was 80 ± 52.7 and 57.7 ± 30.4 min for the high and low dose, respectively. The apparent mean volumes of distribution at steady-state were 7.2 ± 3 and 4.5 ± 2.4 L/kg, while the clearance was 74.7 ± 19 and 68.1 ± 20 mL/kg/min for the high and low doses, respectively. Compared to saline, hydromorphone and morphine produced significant anti-nociception and sedation of similar magnitude for 120 min. In conclusion, intravenous hydromorphone has a large volume of distribution, and high clearance rate that exceeds hepatic blood flow. In dogs, it produced mechanical anti-nociception and sedation of a magnitude similar to morphine.  相似文献   

5.
Six dogs were treated with a single intravenous (i.v.) dose (2 mg/kg) of marbofloxacin, followed by single oral (p.o.) doses of marbofloxacin at 1, 2 and 4 mg/kg, according to a three-way crossover design. The same experimental design was used for the subcutaneous (s.c.) route. In addition, a long-term trial involving eight dogs given oral doses of marbofloxacin at 2, 4 and 6 mg/kg/day for thirteen weeks was carried out. Plasma and urine samples were collected during the first two trials, plasma and skin samples were collected after the second of these trials. Plasma, urine and skin concentrations of marbofloxacin were determined by a reverse phase liquid chromatographic method. Mean pharmacokinetic parameters after i.v. administration were the following: t1/2β=12.4h; Cl B= 0.10 L/h.kg; V area= 1.9 L/kg. The oral bioavailability of marbofloxacin was close to 100% for the three doses. At 2 mg/kg, C max of 1.4 μg/mL was reached at t max of 2.5 h. Mean AUC and C max values had a statistically significant linear relationship with the doses administered. About 40% of the administered dose was excreted in urine as unchanged parent drug. After s.c. administration, the calculated parameters were close to those obtained after oral administration, except t max (about 1 h) which was shorter. The mean skin to plasma concentration ratio after the long-term trial was 1.6, suggesting good tissue penetration of marbofloxacin.  相似文献   

6.
The pharmacokinetics of benazepril, enalapril, and their active metabolites (benazeprilat and enalaprilat) were compared after a single administration of each product by the oral route at the recommended dosage (0.5 mg/kg for both drugs) in the dog before and after moderate experimental renal impairment. Ten dogs were randomly assigned to 2 groups of 5 animals in a 2-period crossover design for angiotensin-converting enzyme inhibitor administration. Renal failure was surgically induced by right nephrectomy and electrocoagulation of the remaining kidney. Renal mass reduction induced a significant decrease (P < .001) in glomerular filtration rate (GFR) (1.7 +/- 0.3 versus 3.3 +/- 0.7 mL/kg/minute). No significant differences before and after surgery were observed for enalapril and benazepril kinetics. The area under the curve (AUC) for enalaprilat increased after surgery from 23.6 +/- 14.7 to 42.4 +/- 20.9 micrograms.minute/mL (P < .01). Mean peak plasma concentration (Cmax) was increased in the impaired dogs (59.1 +/- 23.3 versus 43.9 +/- 32.9 ng/mL), but this variation was not significant (P > .05). Renal failure had no significant effect on AUC for benazeprilat (13.8 +/- 9.8 versus 14.9 +/- 5.0 micrograms.minute/mL) (P > .05), but Cmax decreased significantly (from 55.0 +/- 26.4 to 31.9 +/- 17.7 ng/mL) (P < .05). Multiple regression analysis showed that both GFR and AUC for enalapril were highly significant variables that explained the variation in AUC for enalaprilat (R2 = .86, P < .001) but not for benazeprilat (R2 = .12, P > .05). The results of this study indicate that exposure to enalaprilat, but not to benazeprilat, is increased in dogs with subclinical renal impairment.  相似文献   

7.
Abo-El-Sooud, K., Goudah, A. Influence of Pasteurella multocida infection on the pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in rabbits. J. vet. Pharmacol. Therap. 33 , 63–68.
The pharmacokinetic behavior of marbofloxacin was studied in healthy ( n  = 12) and Pasteurella multocida infected rabbits ( n  = 12) after single intravenous (i.v.) and intramuscular (i.m.) administrations. Six rabbits in each group (control and diseased) were given a single dose of 2 mg/kg body weight (bw) of marbofloxacin intravenously. The other six rabbits in each group were given the same dose of the drug intramuscularly. The concentration of marbofloxacin in plasma was determined using high-performance liquid chromatography. The plasma concentrations were higher in diseased rabbits than in healthy rabbits following both routes of injections. Following i.v. administration, the values of the elimination half-life ( t 1/2β), and area under the curve were significantly higher, whereas total body clearance was significantly lower in diseased rabbits. After i.m. administration, the elimination half-life ( t 1/2el), mean residence time, and maximum plasma concentration ( C max) were higher in diseased rabbits (5.33 h, 7.35 h and 2.24 μg/mL) than in healthy rabbits (4.33 h, 6.81 h and 1.81 μg/mL, respectively). Marbofloxacin was bound to the extent of 26 ± 1.3% and 23 ± 1.6% to plasma protein of healthy and diseased rabbits, respectively. The C max /MIC (minimum inhibitory concentration) and AUC/MIC ratios were significantly higher in diseased rabbits (28 and 189 h) than in healthy rabbits (23 and 157 h), indicating the favorable pharmacodynamic characteristics of the drug in diseased rabbits.  相似文献   

8.
The pharmacokinetics of selamectin were evaluated in cats and dogs, following intravenous (0.05, 0.1 and 0.2 mg/kg), topical (24 mg/kg) and oral (24 mg/kg) administration. Following selamectin administration, serial blood samples were collected and plasma concentrations were determined by high performance liquid chromatography (HPLC). After intravenous administration of selamectin to cats and dogs, the mean maximum plasma concentrations and area under the concentration-time curve (AUC) were linearly related to the dose, and mean systemic clearance (Clb) and steady-state volume of distribution (Vd(ss)) were independent of dose. Plasma concentrations after intravenous administration declined polyexponentially in cats and biphasically in dogs, with mean terminal phase half-lives (t(1/2)) of approximately 69 h in cats and 14 h in dogs. In cats, overall Clb was 0.470 +/- 0.039 mL/min/kg (+/-SD) and overall Vd(ss) was 2.19 +/- 0.05 L/kg, compared with values of 1.18 +/- 0.31 mL/min/kg and 1.24 +/- 0.26 L/kg, respectively, in dogs. After topical administration, the mean C(max) in cats was 5513 +/- 2173 ng/mL reached at a time (T(max)) of 15 +/- 12 h postadministration; in dogs, C(max) was 86.5 +/- 34.0 ng/mL at T(max) of 72 +/- 48 h. Bioavailability was 74% in cats and 4.4% in dogs. Following oral administration to cats, mean C(max) was 11,929 +/- 5922 ng/mL at T(max) of 7 +/- 6 h and bioavailability was 109%. In dogs, mean C(max) was 7630 +/- 3140 ng/mL at T(max) of 8 +/- 5 h and bioavailability was 62%. There were no selamectin-related adverse effects and no sex differences in pharmacokinetic parameters. Linearity was established in cats and dogs for plasma concentrations up to 874 and 636 ng/mL, respectively. Pharmacokinetic evaluations for selamectin following intravenous administration indicated a slower elimination from the central compartment in cats than in dogs. This was reflected in slower clearance and longer t(1/2) in cats, probably as a result of species-related differences in metabolism and excretion. Inter-species differences in pharmacokinetic profiles were also observed following topical administration where differences in transdermal flux rates may have contributed to the overall differences in systemic bioavailability.  相似文献   

9.
Enrofloxacin and marbofloxacin are two veterinary fluoroquinolones used to treat severe bacterial infections in horses. A repeated measures study has been designed to compare their pharmacokinetic parameters, to investigate their bioavailability and to estimate their absorbed fraction and first-pass effect by using plasma, urinary and metabolite data collected from five healthy mares. Clearance and V(d(ss)) were greater for enrofloxacin (mean +/- SD = 6.34 +/- 1.5 mL/min/kg and 2.32 +/- 0.32 L/kg, respectively) than for marbofloxacin (4.62 +/- 0.67 mL/min/kg and 1.6 +/- 0.25 L/kg, respectively). Variance of the AUC(0-inf) of marbofloxacin was lower than that for enrofloxacin, with, respectively, a CV = 15% and 26% intravenously and a CV = 31% and 55% after oral administration. Mean oral bioavailability was not significantly different between marbofloxacin (59%) and enrofloxacin (55%). The mean percentage of the dose eliminated unchanged in urine was significantly higher for marbofloxacin (39.7%) than that for enrofloxacin (3.4%). Absorbed fraction and first-pass effect were only determinable for enrofloxacin, whereas the percentage of the dose absorbed in the portal circulation was estimated to be 78% and the fraction not extracted during the first pass through the liver was 65%. Consequently, the moderate observed bioavailability of enrofloxacin appears to be mainly caused by hepatic first-pass effect.  相似文献   

10.
The pharmacokinetics of indomethacin (1mg/kg) was determined in six adult sheep after intravenous (i.v.) and intramuscular (i.m.) injection. Plasma concentrations were maintained within the therapeutic range (0.3–3.0 μg/mL) from 5 to 50 min after i.v. and from 5 to 60–90 min after i.m. administration. After two trials, indomethacin best fitted an open two-compartment model. The mean (±SD) volumes of distribution at steady state ( V dss) were 4.10 ± 1.40 and 4.21 ± 1.93 L/kg and the mean clearance values ( C lB) were 0.17 ± 0.06 and 0.22 ± 0.12 L/h.kg for i.v. and i.m. routes, respectively. The elimination phase half-lives did not show any significant difference between routes of injection ( t ½β = 17.4 ± 4.6 and 21.25 ± 4.44 h, i.v. and i.m. respectively). After i.m. administration, plasma maximum concentration ( C max =  1.10 ± 0.68 μg/mL) was reached 10 min after dosing; the absorption phase was fast ( K ab = 26 ± 18 h-1) and short ( t ½ab = 2.33 ± 1.51 min) and the mean bioavailability was 91.0 ± 32.8%, although there was considerable interanimal variation. In some individuals, bioavailability was higher than 100%. This fact combined with the slower elimination phase after i.m. than after i.v. administration, could be related with enterohepatic recycling.  相似文献   

11.
The single-dose disposition kinetics of orbifloxacin were determined in clinically normal rabbits ( n  = 6) after intravenous (i.v.), subcutaneous (s.c.) and intramuscular (i.m.) administration of 5 mg/kg bodyweight. Orbifloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. Minimal inhibitory concentrations ( MIC s) assay of orbifloxacin against 30 strains of Staphylococcus aureus from several European countries was performed in order to compute pharmacodynamic surrogate markers. The concentration–time data were analysed by compartmental and noncompartmental kinetic methods. Steady-state volume of distribution ( V ss) and total body clearance ( Cl ) of orbifloxacin after i.v. administration were estimated to be 1.71 ± 0.38 L/kg and 0.91 ± 0.20 L/h·kg, respectively. Following s.c. and i.m. administration orbifloxacin achieved maximum plasma concentrations of 2.95 ± 0.82 and 3.24 ± 1.33 mg/L at 0.67 ± 0.20 and 0.65 ± 0.12 h, respectively. The absolute bio-availabilities after s.c. and i.m. routes were 110.67 ± 11.02% and 109.87 ± 8.36%, respectively. Orbifloxacin showed a favourable pharmacokinetic profile in rabbits. However, on account of the low AUC / MIC and C max/ MIC indices obtained, its use by i.m. and s.c. routes against the S. aureus strains assayed in this study cannot be recommended given the risk of selection of resistant populations.  相似文献   

12.
The objective of this study was to confirm in various breeds of dogs the efficacy and safety of a parturition induction treatment described to be successful in Beagle dogs. Parturition was induced in seven various sized pregnant bitches of different breeds, with 15 mg aglepristone per kg at day 59–61 post-estimated ovulation day, followed 24 h later by 0.15 IU oxytocin per kg subcutaneous injections every 2 h. Two bitches were small-sized bitches (<10 kg), three bitches were large-sized bitches (30–40 kg) and two bitches were giant bitches (>40 kg). The results were compared to a control group (n = 6), in which bitches underwent a natural delivery in the same environmental conditions as the induced group. In the induced group, parturition was successfully induced in 7/7 bitches. The first pup in a litter was born on average 25.9 ± 3.29 h after aglepristone administration (21–30 h). Two of seven bitches from the small-sized group delivered some of their pups before the first administration of oxytocin. The mean duration of parturition was 9.6 ± 5.4 h vs 8.0 ± 4.8 h in the control group. The mean interval between two successive pups being delivered was 115.6 ± 82.8 min (34–265) vs 68.8 ± 24.5 min in the control group (p < 0.03). The mean weight at parturition did not differ significantly between the two groups. One litter of four Yorkshire Terrier pups in the induced group were premature at the time of birth and died between 19 and 29 h post-delivery. This study, although on a very limited number of dogs, confirms the efficacy of the aglepristone/oxytocin protocol to induce parturition in dogs.  相似文献   

13.
Intravenous (IV) levetiracetam (LEV) is available for humans for bridge therapy when the oral route is unavailable. We investigated the safety and pharmacokinetics of LEV administered intramuscularly (IM), IV, and orally to dogs.
Six Hound dogs received 19.5–22.6 mg/kg of LEV IM, IV and orally with a wash-out period in between. All dogs received 500 mg LEV orally and 5 mL of 100 mg/mL LEV IM. Three dogs received 500 mg of LEV IV and three dogs received 250 mg LEV IV with 250 mg given perivascularly to approximate extravasation. Safety was assessed using a pain scale at time of IM administration and histopathological examination 24 h to 5 days after injection.
Intravenous LEV half-life was 180 ± 18 min. Bioavailability of IM LEV was 100%. Mean time to Tmax after IM was 40 ± 16 min. The mean Cmax IM was 30.3 ± 3 μg/mL compared to the C0 of 37 ± 5 μg/mL for IV. Mean inflammation score (0–4 scale) for IM LEV was 0.28 and for saline 0.62. Extravasation did not cause tissue damage.
Parenteral LEV is well tolerated and appears safe following IM and IV injections in dogs. Parenteral LEV should be evaluated for use in dogs with epilepsy.  相似文献   

14.
Cisatracurium undergoes primarily temperature and pH-dependent Hofmann elimination in humans. This study was conducted to describe the pharmacokinetics of cisatracurium in anesthetized dogs and determine whether its in vitro degradation rate in plasma is predictive of its in vivo elimination rate, as this is the case in humans. Nine dogs were anesthetized with pentobarbital and administered different bolus doses of cisatracurium in a randomized cross-over design. Arterial blood was collected at frequent intervals after each bolus injection. In vitro degradation rate ( k in vitro ) of cisatracurium was determined in each dog blank plasma. Plasma concentrations were determined by HPLC. Pharmacokinetic analyses were performed using two compartmental models assuming central or both central and peripheral elimination. Mean in vivo terminal elimination rate of cisatracurium (16.4 ± 2.7 min) was twofold faster than mean in vitro degradation rate (32.9 ± 3.7 min) in our dogs. Organ clearance was 6.12 ± 1.69 mL/min·kg and accounted for 56 ± 12% of the total body clearance. Apparent volume of distribution, an exit site-dependent parameter, averaged 212 or 184 mL/kg whether or not peripheral elimination was accounted for in the model. The in vitro rate of degradation in plasma is not of predictive value for the in vivo elimination rate of cisatracurium in anesthetized dogs. Organ clearance plays a more important role in the elimination of cisatracurium in dogs than in humans. Increased biliary excretion and/or presence of renal secretion are potential mechanisms that need to be explored.  相似文献   

15.
To evaluate the fate and disposition of marbofloxacin (MBF) in freshwater crocodiles (Crocodylus siamensis), MBF was administered either intravenously (i.v.) or intramuscularly (i.m.) at a dosage of 2.0 mg/kg body weight. The concentrations of MBF in plasma were measured using high‐performance liquid chromatography equipped with a fluorescence detector. The concentrations of MBF in the plasma were measurable up to 144 h after i.v. and i.m. administration. After the first 45 min, the mean pharmacokinetic profiles produced by the two administration routes were almost identical. No statistically significant differences in the pharmacokinetic parameters between the groups were observed. The half‐life was long (about 2.5 days), the volume of distribution was large (about 1.44 L/kg), λz was small (0.01 h?1), and the clearance was slow (22.6 mL/h/kg). The absolute i.m. bioavailability (F%) was 105.36%. The dose of MBF administered in this study seems to produce appropriate PK‐PD parameters that predict antibacterial success for disease caused by susceptible bacteria. More studies are warranted to evaluate the likely residues after administration of multiple doses.  相似文献   

16.
An overview of the pharmacokinetics of dirlotapide in beagle dogs is presented. The following mean parameters were observed after a 0.3-mg/kg i.v. dose of dirlotapide: plasma clearance of 7.8 mL/min/kg and volume of distribution of 1.3 L/kg. Following single oral doses of 0.05, 0.3, and 1.0 mg/kg to fed dogs and 0.3 mg/kg to fasted dogs using the commercial formulation, mean C max of 7.5, 46, 97, and 31 ng/mL, respectively, were observed at mean t max of 0.8–2.0 h. AUC and C max increased with increasing dose, but not proportionally. Oral bioavailability was 22–41%. Exposure, as reflected by AUC , was 54% higher in the fed than fasted state. In a 14-day repeated-dose study (0.3 mg/kg dose), the mean accumulation ratio was 3.7. In a 3-month study at doses of 0.4–2.5 mg/kg, accumulation ratios ranged from 2.0 to 6.7 at day 29 and from 1.3 to 4.1 at day 87. In summary, dirlotapide exhibited low clearance, low first-pass metabolism, moderate volume of distribution, low-to-moderate oral bioavailability, a modest food effect, and variable accumulation. Large interanimal variability in systemic exposure was noted for all routes and doses, but there were no consistent sex differences.  相似文献   

17.
The purpose of this study was to evaluate the pharmacokinetics of lidocaine in mature Holstein cows following an inverted L and caudal epidural nerve block. Plasma and milk concentrations were determined using high-performance liquid chromatography assay. Pharmacokinetic parameters were estimated using a noncompartmental method. Following administration via inverted L nerve block, serum Tmax was 0.521 ± 0.226 h and serum Cmax was 572 ± 207 ng/mL. Serum AUC was 1348 ± 335 ng·h/mL. Apparent serum t½β was 4.19 ± 1.69 h and MRT was 5.13 ± 2.33 h with clearance uncorrected for the extent of absorption of 2.75 ± 0.68 L/kg/h. The last measurable time of lidocaine detection in serum was 8.5 ± 1.4 h with a mean concentration of 51 ± 30 ng/mL. Milk Tmax was detected at 1.75 ± 0.46 h with Cmax of 300 ± 139 ng/mL. Milk AUC till the last time was 1869 ± 450 ng·h/mL with the mean AUC milk to AUC serum ratio of 1.439 ± 0.374. The last measurable time of lidocaine detection in milk was 32.5 ± 16.2 h with a mean concentration of 46 ± 30 ng/mL. There was no detectable lidocaine concentration in any samples following caudal epidural administration.  相似文献   

18.
Paracetamol was administered at dosages of 5 mg/kg to camels and 10 mg/kg to goats by the intravenous and intramuscular routes. Parent paracetamol had a significantly slower clearance (21.9 ± 1.4 mL/min.kg vs. 52.8 ± 7.3 mL/min.kg) (P < 0.01) in camels than in goats. In camels the predominant metabolite in plasma was the sulphate, although the ratios of glucuronide:paracetamol and sulphate:paracetamol were similar (5.20 ± 0.50 vs. 6.59 ± 0.51) following intravenous administration. In goats the glucuronide metabolite was the predominant moiety in plasma, and the area under the curve (AUC) of the sulphate was only 3.89% of that of the glucuronide conjugate. The apparent AUC for paracetamol in the camel following intramuscular administration was larger than that following intravenous administration, however, when the bioavailability (F) was determined, with correction for altered half-life, within the animal and between study phases it was 71 ± 17% in goats and 105 ± 26% in camels.  相似文献   

19.
The pharmacokinetic behaviour of marbofloxacin, a new fluoroquinolone antimicrobial agent developed exclusively for veterinary use, was studied in mature horses (n = 5) after single-dose i.v. and i.m. administrations of 2 mg/kg bwt. Drug concentrations in plasma were determined by high performance liquid chromatography (HPLC) and data obtained were subjected to compartmental and noncompartmental kinetic analysis. This compound presents a relatively high volume of distribution (V(SS) = 1.17 +/- 0.18 l/kg), which suggests good tissue penetration, and a total body clearance (Cl) of 0.19 +/- 0.042 l/kgh, which is related to a long elimination half-life (t(1/2beta) = 4.74 +/- 0.8 h and 5.47 +/- 1.33 h i.v. and i.m. respectively). Marbofloxacin was rapidly absorbed after i.m. administration (MAT = 33.8 +/- 14.2 min) and presented high bioavailability (F = 87.9 +/- 6.0%). Pharmacokinetic parameters are not significantly different between both routes of administration (P>0.05). After marbofloxacin i.m. administration, no adverse reactions at the site of injection were observed. Serum CK activity levels 12 h after administration increased over 8-fold (range 3-15) compared with pre-injection levels, but this activity decreased to 3-fold during the 24 h follow-up period. Based on the value of surrogate markers to predict clinical success, Cmax/MIC ratio or AUC/MIC ratio, single daily marbofloxacin dose of 2 mg/kg bwt may not be effective in treating infections in horses caused by pathogens with an MIC > or = 0.25 microg/ml. However, if we use a classical antimicrobial efficacy criteria, marbofloxacin can reach a high plasma peak concentration and maintain concentrations higher than MICs determined for marbofloxacin against most gram-negative veterinary pathogens throughout the administration period. Taking into account the fact that fluoroquinolones are considered to have a concentration-dependent effect and a long postantibiotic effect against gram-negative bacteria, a dose of 2 mg/kg bwt every 24 h could be adequate for marbofloxacin in horses.  相似文献   

20.
The effect of ciclosporin A (CsA) on glucose homeostasis was investigated in 16 dogs with atopic dermatitis by determining plasma glucose, serum fructosamine and insulin concentrations, and serial insulin and glucose concentrations following a glucagon stimulation test, before and 6 weeks after CsA therapy at 5 mg/kg once daily. All dogs completed the study. Following CsA treatment, the median serum fructosamine concentrations were significantly higher (pretreatment 227.5 μmol/L; post-treatment 246.5 μmol/L; P = 0.001; reference range 162-310 μmol/L). Based on analyses of the areas under concentration-time curves (AUC) pre- and post-CsA treatment, plasma glucose concentrations were significantly higher (AUC without baseline correction 31.0 mmol/L/min greater; P = 0.021) and serum insulin concentrations were significantly lower (AUC without baseline correction 217.1 μIU/mL/min lower; P = 0.044) following CsA treatment. Peak glucose concentrations after glucagon stimulation test were significantly higher following CsA treatment (10.75 versus 12.05 mmol/L; P = 0.021), but there was no significant difference in peak serum insulin (52.0 versus 35.0 μIU/mL; P = 0.052). There was a negative correlation between baseline uncorrected insulin AUC and trough serum log CsA concentrations (r = -0.70, P = 0.005). The administration of CsA to dogs with atopic dermatitis leads to disturbances in glucose homeostasis. The clinical significance of this is unclear, but it should be taken into account when considering CsA treatment in dogs that already have such impairments.  相似文献   

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