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Abstract

Objective

To examine, in horses, the disposition and excretion of the active metabolite 6-methoxy-2-naphthylacetic acid (6MNA) of the nonsteroidal anti-inflammatory prodrug nabumetone.

Design

Pharmacokinetic analysis of 6MNA after oral administration of nabumetone and IV administration of 6MNA.

Procedure

Using a crossover design, 5 horses were orally administered 3.7 mg of nabumetone/kg of body weight. After a 3-week washout period, 4 horses were administered 2.5 mg of 6MNA/kg, IV.

Results

Absorption of nabumetone from the gastrointestinal tract and its metabolism to 6MNA had a median appearance half-life of 0.88 hour. The elimination half-life was 11 hours. Area under the plasma concentration time curve for 6MNA after oral administration of nabumetone was 120.6 mg/h/L. A dose of 2.5 mg/kg of 6MNA administered IV resulted in plasma concentration nearly equivalent to that induced by the orally administered dose. Disposition of 6MNA was modeled as a one-compartment, first-order elimination. The area under the plasma concentration time curve for IV administration of 6MNA was 117.0 mg/h/L, and the specific volume of distribution was 0.247 L/kg. The distribution half-life and the elimination half-life were 0.56 and 7.90 hours, respectively. Percentage of total dose recovered in urine for the 36-hour collection period after the oral and IV administrations was 7.4 and 5.3%, respectively.

Conclusions

Metabolism of nabumetone to 6MNA, as reported in other species, also occurs in horses. There were a number of additional metabolites of nabumetone in urine that could not be fully identified and characterized. (Am J Vet Res 1996;57:517–521)

Free access
in American Journal of Veterinary Research

SUMMARY

The absorption kinetics of porcine regular insulin following iv, im, and sc administration were evaluated in 10 dogs with alloxan-induced diabetes mellitus. Plasma immunoreactive insulin (iri) concentrations were evaluated immediately prior to and at 10, 20, 30, 45, 60, 90, 120, 180, and 240 minutes following iv administration; and immediately prior to and every 30 minutes for 2 hours and then every hour for 6 hours following im and sc administration of 0.55 U of porcine regular insulin/kg of body weight. Model-independent pharmacokinetic analysis was performed on each data set.

Plasma iri concentration declined rapidly after iv administration of regular insulin and then returned to baseline iri concentration by 3.2 ± 0.8 hours. The absorption kinetics following iv administration of regular insulin were similar to those found in earlier studies in healthy dogs and human beings.

The im and sc routes of regular insulin administration resulted in a pharmacologic concentration of iri at 30 minutes. The peak mean (± SD) plasma iri concentration was significantly (P < 0.05) greater following sc administratin than it was following im administration of regular insulin (263 ± 185 and 151 ± 71 IμU/ml, respectively). The time of the peak plasma iri concentration (68 ± 31 minutes and 60 ± 30 minutes) and the time to return to baseline plasma iri concentration (5.8 ± 1.2 hours and 5.8 ± 1.3 hours) were not significantly different following sc and im administration of regular insulin, respectively. The absorption kinetics following sc administration of regular insulin were similar to those found in earlier studies in healthy dogs and human beings. The absorption kinetics following im administration of regular insulin differed from those found in earlier studies and was similar to the absorption kinetics of regular insulin administered sc in this study. The reasons for this similarity were not readily apparent.

Free access
in American Journal of Veterinary Research

Abstract

Objective

To evaluate efficacy of florfenicol treatment for bovine mastitis caused by Streptococcus agalactiae, Staphylococcus aureus, nonagalactiae streptococci, coagulase-negative staphylococci, Escherichia coli, Klebsiella sp, and others.

Design

Double blind study with cases randomly assigned to 1 of 2 treatment groups.

Sample Population

861 cows/10 commercial dairy farms.

Procedures

Experimental (750 mg of florfenicol) or control (200 mg of cloxacillin) treatment was administered by intramammary infusion every 12 hours for 3 treatments to all cases. Treatments were randomly assigned, identified only by numerical labels. To retain blinding, the longer withdrawal time was adhered to for all cases. Cases remained in the study only if there was no other treatment. Quarter samples were recultured 14, 21, and 28 days later. If all samples after day 1 were culture negative, the case was defined as cured. If only 1 of the follow-up results was positive, the case was considered cured if the day-28 somatic cell count was < 300,000/ml. Failure of treatment was defined as 2 or more culture-positive follow-up samples.

Results

Florfenicol and cloxacillin did not differ significantly in efficacy versus clinical (n = 85) or subclinical (n = 71) bovine mastitis, or for any etiologic agent (χ2). Overall cure rates for mastitis were: Str agalactiae, 5 of 8 (63%); Sta aureus, 5 of 54 (9%); Streptococcus sp, 16 of 35 (46%); Staphylococcus sp, 7 of 33 (21 %); E coli, 5 of 11 (46%); Klebsiella sp, 3 of 6 (50%); others, 1 of 9 (11%); and all cases, 42 of 156 (27%).

Conclusions

Florfenicol did not offer any advantage over cloxacillin in efficacy against bovine mastitis. Overall cure rates were low. As with most mastitis treatment regimens, poor efficacy may be partly attributable to the short duration of treatment. (Am J Vet Res 1996;57:526–528)

Free access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To determine the effect of age on the pharmacokinetics and pharmacodynamics of flunixin meglumine following IV and transdermal administration to calves.

ANIMALS 8 healthy weaned Holstein bull calves.

PROCEDURES At 2 months of age, all calves received an injectable solution of flunixin (2.2 mg/kg, IV); then, after a 10-day washout period, calves received a topical formulation of flunixin (3.33 mg/kg, transdermally). Blood samples were collected at predetermined times before and for 48 and 72 hours, respectively, after IV and transdermal administration. At 8 months of age, the experimental protocol was repeated except calves received flunixin by the transdermal route first. Plasma flunixin concentrations were determined by liquid chromatography-tandem mass spectroscopy. For each administration route, pharmacokinetic parameters were determined by noncompartmental methods and compared between the 2 ages. Plasma prostaglandin (PG) E2 concentration was determined with an ELISA. The effect of age on the percentage change in PGE2 concentration was assessed with repeated-measures analysis. The half maximal inhibitory concentration of flunixin on PGE2 concentration was determined by nonlinear regression.

RESULTS Following IV administration, the mean half-life, area under the plasma concentration-time curve, and residence time were lower and the mean clearance was higher for calves at 8 months of age than at 2 months of age. Following transdermal administration, the mean maximum plasma drug concentration was lower and the mean absorption time and residence time were higher for calves at 8 months of age than at 2 months of age. The half maximal inhibitory concentration of flunixin on PGE2 concentration at 8 months of age was significantly higher than at 2 months of age. Age was not associated with the percentage change in PGE2 concentration following IV or transdermal flunixin administration.

CONCLUSIONS AND CLINICAL RELEVANCE In calves, the clearance of flunixin at 2 months of age was slower than that at 8 months of age following IV administration. Flunixin administration to calves may require age-related adjustments to the dose and dosing interval and an extended withdrawal interval.

Full access
in American Journal of Veterinary Research

Summary

Cardiovascular and respiratory changes that accompany markedly long periods (12 hours) of halothane anesthesia were characterized. Eight spontaneously breathing horses were studied while they were positioned in left lateral recumbency and anesthetized only with halothane in oxygen maintained at a constant end-tidal concentration of 1.06% (equivalent to 1.2 times the minimal alveolar concentration for horses). Results of circulatory and respiratory measurements during the first 5 hours of constant conditions were similar to those previously reported from this laboratory (ie, a time-related significant increase in systemic arterial blood pressure, cardiac output, stroke volume, left ventricular work, pcv, plasma total solids concentration, and little change in respiratory system function). Beyond 5 hours of anesthesia, arterial blood pressure did not further increase, but remained above baseline. Cardiac output continued to increase, because heart rate significantly (P < 0.05) increased. Peak inspiratory gas flow increased significantly (P < 0.05) in later stages of anesthesia. There was a significant decrease in inspiratory time beginning at 4 hours. Although PaO2 and PaCO2 did not significantly change during the 12 hours of study, P v ̄ O 2 increased significantly (P < 0.05) and progressively with time, beginning 6 hours after the beginning of constant conditions. Metabolic acidosis increased with time (significantly [P < 0.05] starting at 9 hours), despite supplemental iv administered NaHCO3, Plasma concentrations of eicosanoids: 6-ketoprostaglandin F (pgf a stable metabolite of pgi 1), pgf , pge, and thromboxane (TxB2, a stable metabolite of TxA2) were measured in 5 of the 8 horses before and during anesthesia. Significant changes from preanesthetic values were not detected. Dynamic thoracic wall and lung compliances decreased with time.

Free access
in American Journal of Veterinary Research