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1.
OBJECTIVE: To determine the clinical effects and pharmacokinetics of amiodarone after single doses of 5 mg/kg administered orally or intravenously. ANIMALS: 6 healthy adult horses. PROCEDURE: In a cross over study, clinical signs and electrocardiographic variables were monitored and plasma and urine samples were collected. A liquid chromatography-mass spectrometry method was used to determine the percentage of protein binding and to measure plasma and urine concentrations of amiodarone and the active metabolite desethylamiodarone. RESULTS: No adverse clinical signs were observed. After IV administration, median terminal elimination half-lives of amiodarone and desethylamiodarone were 51.1 and 75.3 hours, respectively. Clearance was 0.35 L/kg x h, and the apparent volume of distribution for amiodarone was 31.1 L/kg. The peak plasma desethylamiodarone concentration of 0.08 microg/mL was attained 2.7 hours after IV administration. Neither parent drug nor metabolite was detected in urine, and protein binding of amiodarone was 96%. After oral administration of amiodarone, absorption of amiodarone was slow and variable; bioavailability ranged from 6.0% to 33.7%. The peak plasma amiodarone concentration of 0.14 microg/mL was attained 7.0 hours after oral administration and the peak plasma desethylamiodarone concentration of 0.03 microg/mL was attained 8.0 hours after administration. Median elimination half-lives of amiodarone and desethylamiodarone were 24.1 and 58.6 hours, respectively. CONCLUSION AND CLINICAL RELEVANCE: Results indicate that the pharmacokinetic distribution of amiodarone is multicompartmental. This information is useful for determining treatment regimens for horses with arrythmias. Amiodarone has low bioavailability after oral administration, does not undergo renal excretion, and is highly protein-bound in horses.  相似文献   

2.
OBJECTIVE: To determine pharmacokinetics and excretion of phenytoin in horses. ANIMALS: 6 adult horses. PROCEDURE: Using a crossover design, phenytoin was administered (8.8 mg/kg of body weight, IV and PO) to 6 horses to determine bioavailability (F). Phenytoin also was administered orally twice daily for 5 days to those same 6 horses to determine steady-state concentrations and excretion patterns. Blood and urine samples were collected for analysis. RESULTS: Mean (+/- SD) elimination half-life following a single IV or PO administration was 12.6+/-2.8 and 13.9+/-6.3 hours, respectively, and was 11.2+/-4.0 hours following twice-daily administration for 5 days. Values for F ranged from 14.5 to 84.7%. Mean peak plasma concentration (Cmax) following single oral administration was 1.8+/-0.68 microg/ml. Steady-state plasma concentrations following twice-daily administration for 5 days was 4.0+/-1.8 microg/ml. Of the 12.0+/-5.4% of the drug excreted during the 36-hour collection period, 0.78+/-0.39% was the parent drug phenytoin, and 11.2+/-5.3% was 5-(phydroxyphenyl)-5-phenylhydantoin (p-HPPH). Following twice-daily administration for 5 days, phenytoin was quantified in plasma and urine for up to 72 and 96 hours, respectively, and p-HPPH was quantified in urine for up to 144 hours after administration. This excretion pattern was not consistent in all horses. CONCLUSIONS AND CLINICAL RELEVANCE: Variability in F, terminal elimination-phase half-life, and Cmax following single or multiple oral administration of phenytoin was considerable. This variability makes it difficult to predict plasma concentrations in horses after phenytoin administration.  相似文献   

3.
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   

4.
OBJECTIVE: To determine the pharmacokinetics of enrofloxacin administered IV and orally to foals. ANIMALS: 5 clinically normal foals. PROCEDURE: A 2-dose cross-over trial with IV and oral administration was performed. Enrofloxacin was administered once IV (5 mg/kg of body weight) to 1-week-old foals, followed by 1 oral administration (10 mg/kg) after a 7-day washout period. Blood samples were collected for 48 hours after the single dose IV and oral administrations and analyzed for plasma enrofloxacin and ciprofloxacin concentrations by use of high-performance liquid chromatography. RESULTS: For IV administration, mean +/- SD total area under the curve (AUC0-infinity) was 48.54 +/- 10.46 microg x h/ml, clearance was 103.72 +/- 0.06 ml/kg/h, half-life (t1/2beta) was 17.10 +/- 0.09 hours, and apparent volume of distribution was 2.49 +/- 0.43 L/kg. For oral administration, AUC0-infinity was 58.47 +/- 16.37 microg x h/ml, t1/2beta was 18.39 +/- 0.06 hours, maximum concentration (Cmax) was 2.12 +/- 00.51 microg/ml, time to Cmax was 2.20 +/- 2.17 hours, mean absorption time was 2.09 +/- 0.51 hours, and bioavailability was 42 +/- 0.42%. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with adult horses given 5 mg of enrofloxacin/kg IV, foals have higher AUC0-infinity, longer t1/2beta, and lower clearance. Concentration of ciprofloxacin was negligible. Using a target Cmax to minimum inhibitory concentration ratio of 1:8 to 1:10, computer modeling suggests that 2.5 to 10 mg of enrofloxacin/kg administered every 24 hours would be effective in foals, depending on minimum inhibitory concentration of the pathogen.  相似文献   

5.
OBJECTIVE: To determine pharmacokinetics of single and multiple doses of rimantadine hydrochloride in horses and to evaluate prophylactic efficacy of rimantadine in influenza virus-infected horses. ANIMALS: 5 clinically normal horses and 8 horses seronegative to influenza A. PROCEDURE: Horses were given rimantadine (7 mg/kg of body weight, i.v., once; 15 mg/kg, p.o., once; 30 mg/kg, p.o., once; and 30 mg/kg, p.o., q 12 h for 4 days) to determine disposition kinetics. Efficacy in induced infections was determined in horses seronegative to influenza virus A2. Rimantadine was administered (30 mg/kg, p.o., q 12 h for 7 days) beginning 12 hours before challenge-exposure to the virus. RESULTS: Estimated mean peak plasma concentration of rimantadine after i.v. administration was 2.0 micrograms/ml, volume of distribution (mean +/- SD) at steady-state (Vdss) was 7.1 +/- 1.7 L/kg, plasma clearance after i.v. administration was 51 +/- 7 ml/min/kg, and beta-phase half-life was 2.0 +/- 0.4 hours. Oral administration of 15 mg of rimantadine/kg yielded peak plasma concentrations of < 50 ng/ml after 3 hours; a single oral administration of 30 mg/kg yielded mean peak plasma concentrations of 500 ng/ml with mean bioavailability (F) of 25%, beta-phase half-life of 2.2 +/- 0.3 hours, and clearance of 340 +/- 255 ml/min/kg. Multiple doses of rimantadine provided steady-state concentrations in plasma with peak and trough concentrations (mean +/- SEM) of 811 +/- 97 and 161 +/- 12 ng/ml, respectively. Rimantadine used prophylactically for induced influenza virus A2 infection was associated with significant decreases in rectal temperature and lung sounds. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of rimantadine to horses can safely ameliorate clinical signs of influenza virus infection.  相似文献   

6.
Single-dose pharmacokinetic variables of pyrimethamine were studied in horses. Pyrimethamine (1 mg/kg of body weight) was administered IV and orally to 6 adult horses, and plasma samples were obtained at frequent intervals thereafter. Plasma pyrimethamine concentration was assayed by gas chromatography, and concentration-time data were analyzed, using a pharmacokinetic computer program. The IV and oral administration data were best described by 3-compartment and 1-compartment models, respectively. The median volume of distribution at steady state after IV administration was 1,521 ml/kg and the median elimination half-time was 12.06 hours. Mean plasma concentration after oral administration fluctuated between a maximal concentration of 0.18 microgram/ml and 0.09 microgram/ml (24 hours after dosing). Bioavailability after oral administration was 56%.  相似文献   

7.
OBJECTIVE: To determine the pharmacokinetics of fluconazole in horses. ANIMALS: 6 clinically normal adult horses. PROCEDURE: Fluconazole (10 mg/kg of body weight) was administered intravenously or orally with 2 weeks between treatments. Plasma fluconazole concentrations were determined prior to and 10, 20, 30, 40, and 60 minutes and 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after administration. A long-term oral dosing regimen was designed in which all horses received a loading dose of fluconazole (14 mg/kg) followed by 5 mg/kg every 24 hours for 10 days. Fluconazole concentrations were determined in aqueous humor, plasma, CSF, synovial fluid, and urine after administration of the final dose. RESULTS: Mean (+/- SD) apparent volume of distribution of fluconazole at steady state was 1.21+/-0.01 L/kg. Systemic availability and time to maximum plasma concentration following oral administration were 101.24+/-27.50% and 1.97+/-1.68 hours, respectively. Maximum plasma concentrations and terminal half-lives after IV and oral administration were similar. Plasma, CSF, synovial fluid, aqueous humor, and urine concentrations of fluconazole after long-term oral administration of fluconazole were 30.50+/-23.88, 14.99+/-1.86, 14.19+/-5.07, 11.39+/-2.83, and 56.99+/-32.87 microg/ml, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Bioavailability of fluconazole was high after oral administration to horses. Long-term oral administration maintained plasma and body fluid concentrations of fluconazole above the mean inhibitory concentration (8.0 mg/ml) reported for fungal pathogens in horses. Fluconazole may be an appropriate agent for treatment of fungal infections in horses.  相似文献   

8.
OBJECTIVE: To determine the pharmacokinetics of voriconazole following IV and PO administration and assess the distribution of voriconazole into body fluids following repeated PO administration in horses. ANIMALS: 6 clinically normal adult horses. PROCEDURES: All horses received voriconazole (10 mg/kg) IV and PO (2-week interval between treatments). Plasma voriconazole concentrations were determined prior to and at intervals following administration. Subsequently, voriconazole was administered PO (3 mg/kg) twice daily for 10 days to all horses; plasma, synovial fluid, CSF, urine, and preocular tear film concentrations of voriconazole were then assessed. RESULTS: Mean +/- SD volume of distribution at steady state was 1,604.9 +/- 406.4 mL/kg. Systemic bioavailability of voriconazole following PO administration was 95 +/- 19%; the highest plasma concentration of 6.1 +/- 1.4 microg/mL was attained at 0.6 to 2.3 hours. Mean peak plasma concentration was 2.57 microg/mL, and mean trough plasma concentration was 1.32 microg/mL. Mean plasma, CSF, synovial fluid, urine, and preocular tear film concentrations of voriconazole after long-term PO administration were 5.163 +/- 1.594 microg/mL, 2.508 +/- 1.616 microg/mL, 3.073 +/- 2.093 microg/mL, 4.422 +/- 0.8095 microg/mL, and 3.376 +/- 1.297 microg/mL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that voriconazole distributed quickly and widely in the body; following a single IV dose, initial plasma concentrations were high with a steady and early decrease in plasma concentration. Absorption of voriconazole after PO administration was excellent, compared with absorption after IV administration. Voriconazole appears to be another option for the treatment of fungal infections in horses.  相似文献   

9.
The pharmacokinetics and estimated bioavailability of amoxicillin were determined after IV, intragastric, and IM administration to healthy mares. After IV administration of sodium amoxicillin (10 mg/kg of body weight), the disposition of the drug was best described by a 2-compartment open model. A rapid distribution phase was followed by a rapid elimination phase, with a mean +/- SD half-life of 39.4 +/- 3.57 minutes. The mean volume of distribution was 325 +/- 68.2 ml/kg, and the mean body clearance was 5.68 +/- 0.80 ml/min.kg. It was concluded that frequent IV administration of sodium amoxicillin would be required to maintain therapeutic plasma concentrations of amoxicillin, and thus, the use of this dosage form should be limited to the initiation of treatment or to intensive care situations. After intragastric administration of amoxicillin trihydrate (20 mg/kg), 5% cherry-flavored suspension, the drug was rapidly, but incompletely, absorbed and rapidly eliminated (mean half-life of the decline phase of the plasma amoxicillin concentration-time curve, 51 minutes). The mean estimated bioavailability (fractional absorption) of the administered dose was 10.4%, and the mean peak plasma amoxicillin concentration was 2.73 micrograms/ml at 1.5 hours after dosing. In one horse with clinical signs of abdominal discomfort and diarrhea, the absorption of amoxicillin from the gastrointestinal tract was delayed and the fraction absorbed was increased. It was concluded that this oral dosage form could be recommended only for the treatment of infections caused by bacteria that are highly susceptible to amoxicillin, that frequent dosing would be necessary, and that absorption may be inconsistent in horses with gastrointestinal disease.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

10.
OBJECTIVE: To characterize pharmacokinetics of voriconazole in horses after oral and IV administration and determine the in vitro physicochemical characteristics of the drug that may affect oral absorption and tissue distribution. ANIMALS: 6 adult horses. PROCEDURES: Horses were administered voriconazole (1 mg/kg, IV, or 4 mg/kg, PO), and plasma concentrations were measured by use of high-performance liquid chromatography. In vitro plasma protein binding and the octanol:water partition coefficient were also assessed. RESULTS: Voriconazole was adequately absorbed after oral administration in horses, with a systemic bioavailability of 135.75 +/- 18.41%. The elimination half-life after a single orally administered dose was 13.11 +/- 2.85 hours, and the maximum plasma concentration was 2.43 +/- 0.4 microg/mL. Plasma protein binding was 31.68%, and the octanol:water partition coefficient was 64.69. No adverse reactions were detected during the study. CONCLUSIONS AND CLINICAL RELEVANCE: Voriconazole has excellent absorption after oral administration and a long half-life in horses. On the basis of the results of this study, it was concluded that administration of voriconazole at a dosage of 4 mg/kg, PO, every 24 hours will attain plasma concentrations adequate for treatment of horses with fungal infections for which the fungi have a minimum inhibitory concentration 相似文献   

11.
OBJECTIVE: To study the pharmacokinetics of difloxacin (5 mg/kg) following IV, IM, and intragastric (IG) administration to healthy horses. ANIMALS: 6 healthy mature horses. PROCEDURES: A crossover study design with 3 phases was used (15-day washout periods between treatments). An injectable formulation of difloxacin (5%) was administered IV and IM in single doses (5 mg/kg); for IG administration, an oral solution was prepared and administered via nasogastric tube. Blood samples were collected before and at intervals after each administration. A high-performance liquid chromatography assay with fluorescence detection was used to determine plasma difloxacin concentrations. Pharmacokinetic parameters of difloxacin were analyzed. Plasma creatine kinase activity was monitored to assess tissue damage. RESULTS: Difloxacin plasma concentration versus time data after IV administration were best described by a 2-compartment open model. The disposition of difloxacin following IM or IG administration was best described by a 1-compartment model. Mean half-life for difloxacin administered IV, IM, and IG was 2.66, 5.72, and 10.75 hours, respectively. Clearance after IV administration was 0.28 L/kg.h. After IM administration, the absolute mean +/- SD bioavailability was 95.81 +/- 3.11% and maximum plasma concentration (Cmax) was 1.48 +/- 0.12 mg/L. After IG administration, the absolute bioavailability was 68.62 +/- 10.60% and Cmax was 0.732 +/- 0.05 mg/L. At 12 hours after IM administration, plasma creatine kinase activity had increased 7-fold, compared with the preinjection value. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggest that difloxacin is likely to be effective for treating susceptible bacterial infections in horses.  相似文献   

12.
OBJECTIVE: To determine pharmacokinetics and metabolic patterns of fenbendazole after IV and oral administration to pigs. ANIMALS: 4 mixed-breed female pigs weighing 32 to 45 kg. PROCEDURE: Fenbendazole was administered IV at a dose of 1 mg/kg. One week later, it was administered orally at a dose of 5 mg/kg. Blood samples were collected for up to 72 hours after administration, and plasma concentrations of fenbendazole, oxfendazole, and fenbendazole sulfone were determined by use of high-pressure liquid chromatography. Plasma pharmacokinetics were determined by use of noncompartmental methods. RESULTS: Body clearance of fenbendazole after IV administration was 1.36 L/h/kg, volume of distribution at steady state was 3.35 L/kg, and mean residence time was 2.63 hours. After oral administration, peak plasma concentration of fenbendazole was 0.07 microg/ml, time to peak plasma concentration was 3.75 hours, and mean residence time was 15.15 hours. Bioavailability of fenbendazole was 27.1%. Oxfendazole was the major plasma metabolite, accounting for two-thirds of the total area under the plasma concentration versus time curve after IV and oral administration. Fenbendazole accounted for 8.4% of the total AUC after IV administration and 4.5% after oral administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that fenbendazole was rapidly eliminated from plasma of pigs. The drug was rapidly absorbed after oral administration, but systemic bioavailability was low.  相似文献   

13.
The pharmacokinetics of spiramycin in pigs were investigated after intravenous and oral administration. The potential therapeutically effective blood level was established after a single administration and examined in a subsidiary five day study. The rapid intravenous injection of 25 mg spiramycin/kg bodyweight produced marked salivation in all the test animals. The elimination half-life (2.3 +/- 1.2 hours) was relatively short, in accordance with the total body clearance rate (27.3 +/- 10.1 ml/minute/kg). The high volume of distribution (5.2 +/- 2.2 litres/kg) was due to the accumulation of the drug in the body tissues. The maximum plasma concentration (4.1 +/- 1.7 micrograms/ml) after oral administration of 85 to 100 mg spiramycin/kg bodyweight was reached after 3.7 +/- 0.8 hours and the half-life of the elimination phase was 6.0 +/- 2.4 hours. The oral bioavailability was 45.4 +/- 23.4 per cent. Ad libitum feeding of a diet containing 2550 mg spiramycin/kg produced a steady state concentration of 0.96 +/- 0.27 micrograms/ml. This plasma concentration would provide a potentially therapeutically effective blood concentration against Mycoplasma species, Streptococcus species and Staphylococcus species.  相似文献   

14.
Six mature Holstein bulls were each given 10 mg of phenylbutazone (PBZ)/kg of body weight, PO. Of the 6 bulls, 3 were given 10 mg of PBZ/kg by rapid IV administration 4 weeks later. Plasma concentration-vs-time data were analyzed, using nonlinear regression modeling (sum of exponential functions). The harmonic mean of the biologic half-life of PBZ was 62.6 +/- 12.9 hours after oral administration and 61.6 +/- 7.2 hours after IV administration. The mean residence time was 94.61 +/- 8.44 hours and 90.49 +/- 8.93 hours for oral and IV administration, respectively. The mean total body clearance was 0.0015 +/- 0.0003 L/h/kg, with the mean apparent volume of distribution 0.134 +/- 0.021 L/kg. Mean bioavailability was 73 +/- 2% after oral administration. Phenylbutazone was adequately absorbed from the gastrointestinal tract in bulls. The apparent volume of distribution was small, indicating that PBZ distributed mainly into plasma and extracellular fluid. The total body clearance was also small, which accounted for the long half-life of PBZ in bulls.  相似文献   

15.
OBJECTIVE: To determine pharmacokinetic parameters for meloxicam, a nonsteroidal anti-inflammatory drug, in horses. ANIMALS: 8 healthy horses. PROCEDURE: In the first phase of the study, horses were administered meloxicam once in accordance with a 2 x 2 crossover design (IV or PO drug administration; horses fed or not fed). The second phase used a multiple-dose regimen (daily oral administration of meloxicam for 14 days), with meloxicam administered at the recommended dosage (0.6 mg/kg). Plasma and urine concentrations of meloxicam were measured by use of validated methods with a limit of quantification of 10 ng/mL for plasma and 20 ng/mL for urine. RESULTS: Plasma clearance was low (mean +/- SD; 34 +/- 0.5 mL/kg/h), steady-state volume of distribution was limited (0.12 +/- 0.018 L/kg), and terminal half-life was 8.54 +/- 3.02 hours. After oral administration, bioavailability was nearly total regardless of feeding status (98 +/- 12% in fed horses and 85 +/- 19% in nonfed horses). During once-daily administration for 14 days, we did not detect drug accumulation in the plasma. Meloxicam was eliminated via the urine with a urine-to-plasma concentration that ranged from 13 to 18. Concentrations were detected for a relatively short period (3 days) after administration of the final daily dose. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study support once-daily administration of meloxicam regardless of the feeding status of a horse and suggest a period of at least 3 days before urine concentrations of meloxicam reach concentrations that could be used in drug control programs.  相似文献   

16.
OBJECTIVE: To assess bioequivalence after oral, IM, and IV administration of racemic ketoprofen in pigs and to investigate the bioavailability after oral and IM administration. ANIMALS: 8 crossbred pigs. PROCEDURES: Each pig received 4 treatments in a randomized crossover design, with a 6-day washout period. Ketoprofen was administered at 3 and 6 mg/kg, PO; 3 mg/kg, IM; and 3 mg/kg, IV. Plasma ketoprofen concentrations were measured by use of high-performance liquid chromatography for up to 48 hours. To assess bioequivalence, a 90% confidence interval was calculated for the area under the time-concentration curve (AUC) and maximum plasma concentration (C(max)). RESULTS: Equivalence was not detected in the AUCs among the various routes of administration nor in C(max) between oral and IM administration of 3 mg/kg. The bioavailability of ketoprofen was almost complete after each oral or IM administration. Mean +/- SD C(max) was 5.09 +/- 1.41 microg/mL and 7.62 +/- 1.22 microg/mL after oral and IM doses of 3 mg/kg, respectively. Mean elimination half-life varied from 3.52 +/- 0.90 hours after oral administration of 3 mg/kg to 2.66 +/- 0.50 hours after IV administration. Time to peak C(max) after administration of all treatments was approximately 1 hour. Increases in AUC and C(max) were proportional when the orally administered dose was increased from 3 to 6 mg/kg. Conclusions and Clinical Relevance: Orally administered ketoprofen was absorbed well in pigs, although bioequivalence with IM administration of ketoprofen was not detected. Orally administered ketoprofen may have potential for use in treating pigs.  相似文献   

17.
Norfloxacin was given to 2 groups of chickens (8 chickens/group) at a dosage of 8 mg/kg of body weight, IV and orally. For 24 hours, plasma concentration was monitored serially after each administration. Another group of chickens (n = 30) was given 8 mg of norfloxacin/kg orally every 24 hours for 4 days, and plasma and tissue concentrations of norfloxacin and its major metabolites desethylenenorfloxacin and oxonorfloxacin were determined serially after the last administration of the drug. Plasma and tissue concentrations of norfloxacin, desethylenenorfloxacin, and oxonorfloxacin were measured by use of high-performance liquid chromatography. Pharmacokinetic variables were calculated, using a 2-compartment open model. For norfloxacin, the elimination half-life (t1/2 beta) and the mean +/- SEM residence time for plasma were 12.8 +/- 0.59 and 15.05 +/- 0.81 hours, respectively, after oral administration and 8.0 +/- 0.3 and 8.71 +/- 0.23 hours, respectively, after IV administration. After single oral administration, norfloxacin was absorbed rapidly, with Tmax of 0.22 +/- 0.02 hour. Maximal plasma concentration was 2.89 +/- 0.20 microgram/ml. Oral bioavailability of norfloxacin was found to be 57.0 +/- 2.4%. In chickens, norfloxacin was mainly converted to desethylenenorfloxacin and oxonorfloxacin. Norfloxacin parent drug and its 2 major metabolites were widely distributed in tissues. Considerable tissue concentrations of norfloxacin, desethylenenorfloxacin, and oxonorfloxacin were found when norfloxacin was administered orally (8 mg/kg on 4 successive days). The concentration of the parent fluoroquinolone in fat, kidneys, and liver was 0.05 micrograms/g on day 12 after the end of dosing.  相似文献   

18.
The plasma concentrations and pharmacokinetics of rifampin disposition were determined after a single IV, IM, or oral dose of 10 mg/kg of body weight and an oral dose of 25 mg/kg. The overall elimination rate constants per minute were similar for the 10 mg/kg dose (0.0021 +/- 0.0004, IV; 0.0017 +/- 0.0002, IM; and 0.0023 +/- 0.0006, orally). The apparent bioavailability was moderate to low for IM and oral administrations (59.8% +/- 3.2% and 39.5% +/- 5.0%, respectively). The rate of absorption was most rapid for oral administration with an absorption half-life of 249.7 +/- 71.6 minutes as compared with 403.5 +/- 89.7 minutes for IM administration. However, the IM route produced longer detectable plasma concentrations (50 hours in 2 of the 4 horses). Based on bacterial sensitivity information derived for human and canine isolates, the daily oral administration of 10 mg of rifampin/kg administered in the feed represents a reasonable dose for susceptible gram-positive bacterial pathogens. Higher doses (greater than or equal to 25 mg/kg) or IV administration would be required for most gram-negative bacteria. Adverse effects of sufficient severity to limit use of the drug, especially by the oral route of administration, were not encountered under the single-dose experimental conditions used.  相似文献   

19.
Serum and peritoneal fluid concentrations of metronidazole were determined in 6 healthy adult horses given the drug (25 mg/kg) by IV or oral routes. The disposition of metronidazole in horses given the drug by the IV route conformed to a 2-compartment model with a distribution half-life of 0.16 hours, an elimination half-life of 2.9 hours, and a body clearance of 0.40 +/- 0.05 L/kg/hr. The oral absorption half-life was 0.40 hours, and the bioavailability, 85.0 +/- 18.6%. Peritoneal fluid concentrations were approximately equal to serum concentrations at all times, regardless of the route of administration. On the basis of reported minimal inhibitory concentrations for anaerobic bacteria, a dosage of 15 to 25 mg/kg given orally 4 times daily was recommended.  相似文献   

20.
OBJECTIVE: To compare pharmacokinetics of enrofloxacin administered IV and in various oral preparations to ewes. ANIMALS: 5 mature Katahdin ewes weighing 42 to 50 kg. PROCEDURE: Ewes received 4 single-dose treatments of enrofloxacin in a nonrandomized crossover design followed by a multiple-dose oral regimen. Single-dose treatments consisted of an IV bolus of enrofloxacin (5 mg/kg), an oral drench (10 mg/kg) made from crushed enrofloxacin tablets, oral administration in feed (10 mg/kg; mixture of crushed enrofloxacin tablets and grain), and another type of oral administration in feed (10 mg/kg; mixture of enrofloxacin solution and grain). The multiple-dose regimen consisted of feeding a mixture of enrofloxacin solution and grain (10 mg/kg, q 24 h, for 7 days). Plasma concentrations of enrofloxacin and ciprofloxacin were measured by use of high-performance liquid chromatography. RESULTS: Harmonic mean half-life for oral administration was 14.80, 10.80, and 13.07 hours, respectively, for the oral drench, crushed tablets in grain, and enrofloxacin solution in grain. Oral bioavailability for the oral drench, crushed tablets in grain, and enrofloxacin in grain was 4789, 98.07, and 94.60%, respectively, and median maximum concentration (Cmax) was 1.61, 2.69, and 2.26 microg/ml, respectively. Median Cmax of the multiple-dose regimen was 2.99 microg/ml. CONCLUSIONS AND CLINICAL RELEVANCE: Enrofloxacin administered orally to sheep has a prolonged half-life and high oral bioavailability. Oral administration at 10 mg/kg, q 24 h, was sufficient to achieve a plasma concentration of 8 to 10 times the minimum inhibitory concentration (MIC) of any microorganism with an MIC < or = 0.29 microg/ml.  相似文献   

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