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1.
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   

2.
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   

3.
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   

4.
The effect of an oral dose of probenecid on the disposition kinetics of ampicillin was determined in four horses. An intravenous bolus dose (10 mg/kg) of ampicillin sodium was administered to the horses on two occasions. On the first occasion the antibiotic was administered on its own, and on the second occasion it was administered one hour after an oral dose of 75 mg/kg probenecid. The plasma concentration of probenecid reached a mean (+/- se) maximum concentration (Cmax) of 188-6 +/- 19.3 micrograms/ml after 120.0 +/- 21.2 minutes and concentrations greater than 15 micrograms/ml were present 25 hours after it was administered. The disposition kinetics of ampicillin were altered by the presence of probenecid and as a result the antibiotic had a slower body clearance (ClB; 109.4 +/- 6.71 ml/kg hours compared with 208.9 +/- 26.2 ml/kg hours) a longer elimination half-life (t1/2 beta 1.198 hours compared with 0.701 hours) and consequently a larger area under the plasma concentration versus time curve (AUC 92.3 +/- 5.09 mg/ml hours compared with 35.95 +/- 3.45 mg/ml hours) when compared with animals to which ampicillin was administered alone. The ampicillin concentrations observed suggest that the dosing interval for horses may be increased from between six and eight hours to 12 hours when probenecid is administered in conjunction with the ampicillin.  相似文献   

5.
OBJECTIVE: To determine the pharmacokinetics of acetazolamide administered IV and orally to horses. ANIMALS: 6 clinically normal adult horses. PROCEDURE: Horses received 2 doses of acetazolamide (4 mg/kg of body weight, IV; 8 mg/kg, PO), and blood samples were collected at regular intervals before and after administration. Samples were assayed for acetazolamide concentration by high-performance liquid chromatography, and concentration-time data were analyzed. RESULTS: After IV administration of acetazolamide, data analysis revealed a median mean residence time of 1.71 +/- 0.90 hours and median total body clearance of 263 +/- 38 ml/kg/h. Median steady-state volume of distribution was 433 +/- 218 ml/kg. After oral administration, mean peak plasma concentration was 1.90 +/- 1.09 microg/ml. Mean time to peak plasma concentration was 1.61 +/- 1.24 hours. Median oral bioavailability was 25 +/- 6%. CONCLUSIONS AND CLINICAL RELEVANCE: Oral pharmacokinetic disposition of acetazolamide in horses was characterized by rapid absorption, low bioavailability, and slower elimination than observed initially after IV administration. Pharmacokinetic data generated by this study should facilitate estimation of appropriate dosages for acetazolamide use in horses with hyperkalemic periodic paralysis.  相似文献   

6.
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   

7.
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   

8.
Pharmacokinetics of cefotaxime in the domestic cat   总被引：1，自引：0，他引：1  
Cefotaxime was administered as single IV or IM dose for the purpose of examining its pharmacokinetics in healthy cats. The mean predicted plasma concentration of cefotaxime in 6 cats at 0 time after a single IV dosage of 10 mg/kg of body weight was 88.9 micrograms/ml. The mean plasma concentrations decreased to 10.8 micrograms/ml at 2 hours, 3.7 micrograms/ml at 3 hours, and 0.5 microgram/ml at 6 hours. The half-life was 0.98 +/- 0.25 hour (mean +/- SD), and the total body clearance was determined to be 2.76 +/- 1.25 ml/min/kg. After a single IM injection of 10 mg/kg of body weight, the mean maximum observed plasma concentration was 36.2 micrograms/ml at 0.75 hour. The mean absorption half-life was 0.24 hour. In 2 animals, the bioavailability of an IM injection was 98.2% and 93.0%.  相似文献   

9.
Experiments to determine the residual plasma concentrations of phenylbutazone and its metabolites found in horses racing on a 'no-race day medication' or 24-h rule were carried out. One dosing schedule (oral-i.v.) consisted of 8.8 mg/kg (4 g/1000 lbs) orally for 3 days, followed by 4.4 mg/kg (2 g/1000 lbs) intravenously on day 4. A second schedule consisted of 4.4 mg/kg i.v. for 4 days. The experiments were carried out in Thoroughbred and Standardbred horses at pasture, half-bred horses at pasture, and in Thoroughbred horses in training. After administering the i.v. schedule for 4 days to Thoroughbred and Standardbred horses at pasture, the mean plasma concentrations of phenylbutazone increased from 0.77 microgram/ml on day 2 to 2.5 micrograms/ml on day 5. The shape of the frequency distribution of these populations was log-normal. These data are consistent with one horse in 1,000 yielding a plasma level of 8.07 micrograms/ml on day 5. After administration of the oral-i.v. schedule to Thoroughbred and Standardbred horses at pasture, the mean plasma concentrations of phenylbutazone were 3.4 micrograms/ml on day 2 and 3.5 micrograms/ml on day 5. The range on day 5 was from 1.4 to 8.98 micrograms/ml and the frequency distribution was log-normal. These data are consistent with one horse in 1000 having a plasma level of 15.8 micrograms/ml on day 5. In a final experiment, the oral dosing schedule was administered to 62 Thoroughbred horses in training. Plasma concentrations on day 5 in these horses averaged 5.3 micrograms/ml. The range was from 1.3 to 13.6 micrograms/ml and the frequency distribution was log-normal. Statistical projection of these values suggests that following this oral dosing schedule in racing horses about one horse in 1000 will yield a plasma level of 23.5 micrograms/ml of phenylbutazone 24 h after the last dose.  相似文献   

10.
Doxycycline concentrations, following two types of oral administration to horses, in pulmonary epithelial lining fluid (PELF) were examined and compared to plasma concentrations. The oral bioavailability was estimated from plasma concentrations achieved after an intravenous study in two horses. Doxycycline (10 mg/kg) was administered either intragastric or as topdressing to nonfasted horses. Blood samples were collected for drug analysis, before and 11 times after administration during 24 h. PELF samples were collected by a tampon device four times after drug administration and analysed for doxycycline concentrations. Another two horses received doxycycline intravenously at a dose of 3 mg/kg and plasma was taken 14 times during a 24- h period. The oral bioavailability of doxycycline was calculated to 17% after intragastric administration and 6% after topdressing administration in nonfasted horses. The degree of penetration of doxycycline into PELF, as described by AUC(PELF) /AUC(plasma) ratios, was 0.87 after intragastric administration. The results indicate that clinically relevant doxycycline concentrations are possible to maintain in PELF after intragastric administration. Furthermore, if bioavailability could be enhanced for per os administration, doxycycline might be a valuable drug for the treatment of lower airway infections in horses.  相似文献   

11.
Norfloxacin was given to 6 healthy dogs at a dosage of 5 mg/kg of body weight IV and orally in a complete crossover study, and orally at dosages of 5, 10, and 20 mg/kg to 6 healthy dogs in a 3-way crossover study. For 24 hours, serum concentration was monitored serially after each administration. Another 6 dogs were given 5 mg of norfloxacin/kg orally every 12 hours for 14 days, and serum concentration was determined serially for 12 hours after the first and last administration of the drug. Complete blood count and serum biochemical analysis were performed before and after 14 days of oral norfloxacin administration, and clinical signs of drug toxicosis were monitored twice daily during norfloxacin administration. Urine concentration of norfloxacin was determined periodically during serum acquisition periods. Norfloxacin concentration was determined, using high-performance liquid chromatography with a limit of detection of 25 ng of norfloxacin/ml of serum or urine. Serum norfloxacin pharmacokinetic values after single IV dosing in dogs were best modeled, using a 2-compartment open model, with distribution and elimination half-lives of 0.467 and 3.56 hours (harmonic means), respectively. Area-derived volume of distribution (Vd area) was 1.77 +/- 0.69 L/kg (arithmetic mean +/- SD), and serum clearance (Cls) was 0.332 +/- 0.115 L/h/kg. Mean residence time was 4.32 +/- 0.98 hour. Comparison of the area under the curve (AUC; derived, using model-independent calculations) after iv administration (5 mg/kg) with AUC after oral administration (5 mg/kg) in the same dogs indicated bioavailability of 35.0 +/- 46.1%, with a mean residence time after oral administration of 5.71 +/-2.24 hours. Urine concentration was 33.8 +/- 15.3 micrograms/ml at 4 hours after a single dose of 5 mg/kg given orally, whereas concentration after 20 mg/kg was given orally was 56.8 +/- 18.0 micrograms/ml at 6 hours after dosing. Twelve hours after drug administration, urine concentration was 47.4 +/- 20.6 micrograms/ml after the 5-mg/kg dose and 80.6 +/- 37.7 micrograms/ml after the 20/mg/kg dose.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

12.
Pharmacokinetics and bioavailability of rifampin in adult sheep were investigated by use of high-performance liquid chromatography for determination of serum concentrations. Eight adult ewes were given rifampin PO at the rate of 50 mg of rifampin/kg of body weight. Three weeks after the first experiment, the sheep were given rifampin PO and IV at the rate of 20 mg/kg in a cross-over design, with 1 week between treatments. Serum obtained over a 36-hour period was analyzed for rifampin and a potential metabolite, 25-desacetyl-rifampin, using reverse-phase chromatography with UV detection at 254 nm. Data were analyzed by compartmental and noncompartmental models. Analysis by the noncompartmental model of rifampin serum concentrations after IV administration yielded a mean +/- SD total body clearance of 1.16 +/- 0.21 ml/min/kg, apparent volume of distribution at steady state of 0.45 +/- 0.06 L/kg, and terminal elimination rate constant of 0.15 +/- 0.04 hour-1. The harmonic mean of the elimination half-life was 4.56 hours. Because of incomplete and continuing absorption, bioavailability was extremely variable after oral administration. Desacetyl-rifampin was not detected. On the basis of pharmacokinetic values, serum concentrations measured in this study, and published minimal inhibitory concentrations, the dosage of 20 mg of rifampin/kg, PO, every 24 hours should provide adequate serum concentrations for treatment of rifampin-susceptible bacterial infections in sheep.  相似文献   

13.
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   

14.
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   

15.
Serum concentrations of cefepime (BMY-28142) were determined for four dosing regimes, 10 mg/kg or 20 mg/kg, given as single subcutaneous (SC) or intramuscular injections (IM) to dogs. Serial serum samples were analyzed for the presence of cefepime by high-performance liquid chromatography. In experiment 1, the overall mean (+/- SEM) serum concentration (for a 12-hour period) after a dose of 20 mg/kg for SC and IM routes (4.9 +/- 0.74 micrograms/ml and 5.5 +/- 0.63 micrograms/ml, respectively) was twice that for the 10 mg/kg dose given either SC or IM (2.2 +/- 0.31 micrograms/ml and 2.8 +/- 0.47 micrograms/ml, respectively). There was no significant difference (p greater than 0.05) in mean serum concentrations for SC and IM routes of administration at the same dosage. In subsequent experiments, 5 doses of cefepime (20 mg/kg) were administered IM at 12-hour (experiment 2) or 24-hour (experiment 3) intervals. The mean (+/- SEM) peak serum concentration was 12.1 +/- 1.59 micrograms/ml, 2 hours after the 2nd injection in experiment 2. In experiment 3, the mean (+/- SEM) peak serum concentration was 10.9 +/- 1.34 micrograms/ml, 4 hours after the 1st injection. Mean trough concentrations in experiment 2 were greater than or equal to 0.5 microgram/ml and less than or equal to 0.5 in experiment 3. Multiple IM doses produced transient edema at the injection site and mild lameness in all dogs. Cefepime was highly active against single canine isolates of Staphylococcus intermedius, Pseudomonas aeruginosa and Escherichia coli, with minimum inhibitory concentrations of 0.125 microgram/ml, 1 microgram/ml and 0.3 microgram/ml, respectively.  相似文献   

16.
Oxytetracycline (OTC) concentration in plasma and tissues, plasma pharmacokinetics, depletion from tissue, and toxicity were studied in 30 healthy calves after IM administration of a long-acting OTC preparation (40 mg/kg of body weight) at double the label dosage (20 mg/kg). Plasma OTC concentration increased rapidly after drug administration, and by 2 hours, mean (+/- SD) values were 7.4 +/- 2.6 micrograms/ml, Peak plasma OTC concentration was 9.6 +/- 2.6 micrograms/ml, and the time to peak plasma concentration was 7.6 +/- 4.0 hours. Plasma OTC concentration decreased slowly for 168 hours (elimination phase) after drug administration, and the elimination half-life was 23.9 hours. Plasma OTC concentration exceeded 3.8 micrograms/ml at 48 hours after drug administration. From 168 to 240 hours after drug administration, plasma OTC concentration decreased at a slower rate than that seen during the elimination phase. This slower phase was termed the depletion phase, and the depletion half-life was 280.7 hours. Tissue OTC concentration was highest in kidneys and liver. Lung OTC concentration exceeded 4.4 micrograms/g of tissue and 2.0 micrograms/g of tissue at 12 and 48 hours after drug administration, respectively. The drug persisted the longest in kidneys and liver. At 42 days after drug administration, 0.1 micrograms of OTC/g of kidney was detected. At 49 days after drug administration, all OTC tissue concentrations were below the detectable limit. Reactions and toxicosis after drug administration were limited to an anaphylaxis-like reaction (n = 1) and injection site swellings (n = 2).  相似文献   

17.
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   

18.
Vancomycin was administered IV to healthy adult female dogs at a dosage of 15 mg/kg of body weight every 12 hours for 10 days. Pharmacokinetic values were determined after the first and last doses. The disposition of vancomycin was not altered by multiple dosing, and little accumulation attributable to multiple dosing was observed. Serum vancomycin concentration after the first and last dose were described, using a 2-compartment open model with first-order elimination. The distribution and elimination half-lives after the single dose were 15.4 +/- 2.7 minutes and 137 +/- 21.8 minutes (geometric mean +/- pseudo-SD), respectively; whereas the distribution and elimination half-lives after the last dose were 11.3 +/- 2.61 minutes and 104 +/- 11.2 minutes, respectively. The mean (+/- SD) area-derived volume of distribution was 396 +/- 156 ml/kg and 382 +/- 160 ml/kg after the first and last dose, respectively. Serum vancomycin clearance was 2.13 +/- 0.35 ml/min/kg and 2.49 +/- 0.79 ml/min/kg after the first and last dose, respectively, and 25 to 49% of the total dose of vancomycin was recovered in the urine in the first 24 hours after the single dose administered IV. Mean serum vancomycin concentration reached 101.8 +/- 30.6 micrograms/ml and 99.7 +/- 28.0 micrograms/ml at 5 minutes after a single dose and the last of the multiple doses, respectively, and decreased to 0.94 +/- 0.58 microgram/ml and 1.51 +/- 1.44 micrograms/ml, respectively, at 12 hours after administration. The side effects that accompany vancomycin treatment in human beings were not observed in the dogs; all remained healthy through the end of the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

19.
Gentamicin sulfate (2.2 mg/kg of body weight, IV) was given to anesthetized horses. Jejunal and large colon tissue samples (1 g), serum, and urine were collected over a 4-hour period. Maximum gentamicin concentrations in serum (10.06 +/- 2.85 micrograms/ml) occurred at 0.25 hours after injection. Maximum gentamicin concentrations in the large colon (4.13 +/- 1.80 micrograms/ml) and jejunum (2.26 +/- 1.35 micrograms/ml) occurred in horses at 0.5 and 0.33 hours, respectively. Tissue concentrations decreased in parallel with serum concentrations and were still detectable at the end of the 4-hour period. During the time that samples were collected, the total amount of gentamicin excreted in the urine ranged from 7.21 +/- 3.11 mg to 11.91 +/- 7.12 mg, with a mean urinary concentration of 57.01 +/- 5.37 micrograms/ml. Over the 4-hour collection period, the fraction of dose that was excreted unchanged in the urine was 4.8 +/- 1.9%. Pharmacokinetic analyses of the serum concentration-time data gave a serum half-life of 2.52 +/- 1.29 hours, volume of distribution of 227 +/- 83 ml/kg, and body clearance of 1.12 +/- 0.26 ml/min/kg. The half-lives of the antibiotic in the jejunum and large colon were 1.32 and 1.33 hours, respectively.  相似文献   

20.
OBJECTIVE: To validate use of high-performance liquid chromatography (HPLC) in determining imipramine concentrations in equine serum and to determine pharmacokinetics of imipramine in narcoleptic horses. ANIMALS: 5 horses with adult-onset narcolepsy. PROCEDURE: Blood samples were collected before (time 0) and 3, 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 3, 4, 6, 8, 12, and 24 hours after IV administration of imipramine hydrochloride (2 or 4 mg/kg of body weight). Serum was analyzed, using HPLC, to determine imipramine concentration. The serum concentration-versus-time curve for each horse was analyzed separately to estimate pharmacokinetic values. RESULTS: Adverse effects (muscle fasciculations, tachycardia, hyperresponsiveness to sound, and hemolysis) were detected in most horses when serum imipramine concentrations were high, and these effects were most severe in horses receiving 4 mg of imipramine/kg. Residual adverse effects were not apparent. Value (mean +/- SD) for area under the curve was 3.9 +/- 0.7 h X microg/ml, whereas volume of distribution was 584 +/- 161.7 ml/kg, total body clearance was 522 +/- 102 ml/kg/h, and mean residence time was 1.8 +/- 0.6 hours. One horse had signs of narcolepsy 6 and 12 hours after imipramine administration; corrresponding serum imipramine concentrations were less than the therapeutic range. CONCLUSIONS AND CLINICAL RELEVANCE: Potentially serious adverse effects may be seen in horses administered doses of imipramine that exceed a dosage of 2 mg/kg. Total body clearance of imipramine in horses is slower than that in humans; thus, the interval between subsequent doses should be longer in horses.  相似文献   

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