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  • Author or Editor: Jane Alcorn x
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A cross-over study was performed in 6 healthy mixed-breed dogs and 4 healthy Beagles. Diazepam was administered per rectum to Beagles (0.5 mg/kg of body weight) and mixed-breed dogs (2 mg/kg), and iv (0.5 mg/kg) to both groups of dogs. Each dog received the drug by both routes, with a 1-week washout period between dosages. After diazepam administration, blood samples were collected to measure plasma concentration of diazepam and its active metabolites, desmethyldiazepam and oxazepam, by use of reverse-phase high-performance liquid chromatography (hplc). Systemic availability was assessed by comparing the area under the curve for diazepam metabolites for each route of administration. Mean (± sd) diazepam concentrations in plasma after rectal administration were low in comparison with those obtained after iv administration, with systemic availability of only 7.4 (± 5.9) and 2.7 (± 3.2)% for the high and low dose, respectively. However, diazepam was converted to its metabolites within minutes after administration. Accounting for the total concentration of benzodiazepines (diazepam plus desmethyldiazepam and oxazepam) in plasma, systemic availability was 79.9 (± 20.7) and 66.0 (± 23.8)% for the high and low dosage, respectively. After iv administration, diazepam concentration decreased, with a half-life of only 14 to 16 minutes, but desmethyldiazepam and oxazepam concentrations decreased more slowly, with a half-life of 2.2 to 2.8 hours and 3.5 to 5.1 hours, respectively.

Each of the metabolites is reported to have anticonvulsant activity. After rectal administration of the high dose, mean total benzodiazepine concentration was above 1.0 μg/ml within 10 minutes and was maintained above this concentration for at least 6 hours. We conclude that diazepam is absorbed after rectal administration in dogs, and that the pharmacologic effects are probably caused by the active metabolites, not the parent drug. Samples also were analyzed by use of a nonspecific commercial benzodiazepine fluorescence polarization immunoassay (fpia). Correlation between the fpia and hplc assay was strongest for diazepam (R 2 = 0.84), weak for desmethyldiazepam (R 2 = 0.09), and nonexistent for oxazepam. We conclude from a comparison of assays that hplc is preferred over the fpia method for measuring benzodiazepines in dogs.

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in American Journal of Veterinary Research


OBJECTIVE To investigate the pharmacokinetics of metformin hydrochloride in healthy dogs after IV and oral bolus administrations and determine the oral dose of metformin that yields serum concentrations equivalent to those thought to be effective in humans.

ANIMALS 7 healthy adult mixed-breed dogs.

PROCEDURES Each dog was given a single dose of metformin IV (mean ± SD dose, 24.77 ± 0.60 mg/kg) or PO (mean dose, 19.14 ± 2.78 mg/kg) with a 1-week washout period between treatments. For each treatment, blood samples were collected before and at intervals up to 72 hours after metformin administration. Seventy-two hours after the crossover study, each dog was administered metformin (mean dose, 13.57 ± 0.55 mg/kg), PO, twice daily for 7 days. Blood samples were taken before treatment initiation on day 0 and immediately before the morning drug administration on days 2, 4, 6, and 7. Serum metformin concentrations were determined by means of a validated flow injection analysis–tandem mass spectrometry method.

RESULTS After IV or oral administration to the 7 dogs, there was high interindividual variability in mean serum metformin concentrations over time. Mean ± SD half-life of metformin following IV administration was 20.4 ± 4.1 hours. The mean time to maximum serum concentration was 2.5 ± 0.4 hours. Mean systemic clearance and volume of distribution were 24.1 ± 7.8 mL/min/kg and 44.8 ± 23.5 L/kg, respectively. The mean oral bioavailability was 31%.

CONCLUSIONS AND CLINICAL RELEVANCE The study data indicated that the general disposition pattern and bioavailability of metformin in dogs are similar to those reported for cats and humans.

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in American Journal of Veterinary Research


Objective—To evaluate the pharmacokinetics and thermal and mechanical antinociceptive effects of a fentanyl constant rate infusion (CRI) in conscious cats.

Animals—8 healthy adult cats.

Procedures—At a ≥ 14-day interval, 7 cats received a loading dose (LD) of fentanyl (5 μg/kg, IV [administered at 0 hours]) followed by fentanyl infusion (5 μg/kg/h, IV) for 2 hours or similar administrations of equivalent volumes of 0.9% saline (NaCl) solution. One cat received only the fentanyl treatment. For both treatments, sedation and adverse events were evaluated and mechanical threshold (MT) and thermal threshold (TT) testing was performed prior to (baseline) and at predetermined times up to 26 hours after LD administration; plasma fentanyl concentrations were determined at similar times when the cats received fentanyl.

Results—Fentanyl induced mild sedation during the infusion. The only adverse effect associated with fentanyl LD administration was profuse salivation (1 cat). Saline solution administration did not significantly change MT or TT over time. For the duration of the CRI, MT and TT differed significantly between treatments, except for TT 1 hour after LD administration. For the fentanyl treatment, MT and TT were significantly higher than baseline at 0.25 to 0.75 hours and at 0.25 to 1 hour, respectively. During the fentanyl CRI, mean ± SD plasma fentanyl concentration decreased from 4.41 ± 1.86 ng/mL to 2.99 ± 1.28 ng/mL and was correlated with antinociception; plasma concentrations < 1.33 ± 0.30 ng/mL were not associated with antinociception.

Conclusions and Clinical Relevance—Fentanyl CRI (5 μg/kg/h) induced mechanical and thermal antinociception in cats.

Full access
in American Journal of Veterinary Research