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  • Author or Editor: Joan M. Buck x
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Summary

Dexamethasone pharmacokinetics was studied in 10 healthy dogs receiving high-dose administration of dexamethasone (dosage, 0.1 mg/kg of body weight, iv), alone or combined with acth (dosage, 0.5 U/kg, iv), or low-dose administration of dexamethasone (dosage, 0.01 mg/kg, iv) in an incomplete cross-over design. Serum samples were obtained at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 720, 1,080, 1,440, 1,920, 2,400, and 2,880 minutes after dexamethasone administration; dexamethasone was measured by radioimmunoassay validated for use in dogs. Dexamethasone pharmacokinetics was adequately described by a two-compartment first-order open model.

Comparison of pharmacokinetics for the low- and high-dose protocols revealed dose dependence; area under the curve, mean residence time, clearance, and volume of distribution increased significantly when dexamethasone dosage increased. The elimination rate constant was significantly (P < 0.05) less, and the elimination half-life significantly greater for the high-dose protocols; however, the distribution rate constant and distribution half-life were not significantly different when high-dose protocols were compared with the low-dose protocol. Dose-dependent increases in volume of distribution and clearance may be related to saturation of protein-binding sites. Concurrent administration of acth did not affect dexamethasone disposition.

Free access
in American Journal of Veterinary Research

SUMMARY

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 μg/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 μg/ml at 6 hours after dosing. Twelve hours after drug administration, urine concentration was 47.4 ± 20.6 μg/ml after the 5-mg/kg dose and 80.6 ± 37.7 μg/ml after the 20-mg/kg dose.

Absorption lag time after oral administration ranged from 0.186 ± 0.103 hour after multiple doses (5 mg/kg) to 0.385 ± 0.254 hour after a single dose of 10 mg/kg. The AUC increased (P < 0.01) as the dose increased. However, AUC per unit dose decreased linearly with dose (P < 0.05), most probably because of a dose-dependent decrease in absorption from the gastrointestinal tract.

Free access
in American Journal of Veterinary Research