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- Author or Editor: Luke A. Wittenburg x
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Abstract
OBJECTIVE
To establish the pharmacokinetics of a single 2-mg oral dose of chlorambucil in cats with indolent lymphoproliferative malignancies.
ANIMALS
24 client-owned cats.
PROCEDURES
Cats were assigned to 1 of 4 groups, with each group having a total of 3 sample collection time points over 12 hours after receiving a single 2-mg oral dose of chlorambucil. Each time point combined to generate 6 full patient plasma chlorambucil concentration-time curves from the 24 cats. Chlorambucil treatment was continued every other day and a single, variably timed sample collection was obtained on day 14. Population parameter estimates were obtained by nonlinear mixed-effects modeling. Covariates investigated included age, sex, baseline serum cobalamin, study location, weight, and body condition score.
RESULTS
Chlorambucil administered orally to cats was found to have a peak plasma concentration of approximately 170 ng/mL (SE, 31.1 ng/mL), percent coefficient of variation (%CV) of 18.4% within 15 minutes, and a terminal half-life of 1.8 hours (SE, 0.21 hour; %CV, 12.4). At the 4-hour mark, a smaller secondary peak in plasma chlorambucil was found. Day 14 samples were similar to those of the initial dose. No covariates showed a significant effect in the population model.
CLINICAL RELEVANCE
In these cats, chlorambucil at a 2-mg dose administered every other day undergoes rapid gastrointestinal absorption and plasma clearance with no drug accumulation between doses. These data are critical to inform future work investigating the association of chlorambucil drug exposure with adverse events and outcome of cats with lymphoproliferative diseases.
Abstract
OBJECTIVE To evaluate the pharmacokinetics and bioavailability of 2 doses of orbifloxacin in rabbits.
ANIMALS 6 healthy purpose-bred adult female New Zealand White rabbits (Oryctolagus cuniculus).
PROCEDURES Each of 3 rabbits received orbifloxacin at either 10 or 20 mg/kg, PO. Then, after a 1-week washout period, they received the same dose IV. Blood samples were collected from each rabbit at 0, 0.25, 0.5, 1, 2, 4, 6, 12, and 24 hours after drug administration. Plasma orbifloxacin concentration was measured with liquid chromatography–tandem mass spectrometry. Pharmacokinetic parameters were determined by noncompartmental analysis for data obtained following PO administration and noncompartmental and compartmental analyses for data obtained following IV administration.
RESULTS Following oral administration, the mean ± SD peak plasma orbifloxacin concentration was 1.66 ± 0.51 μg/mL for rabbits administered the 10 mg/kg dose and 3.00 ± 0.97 μg/mL for rabbits administered the 20 mg/kg dose and was attained at 2 hours after drug administration. The mean ± SD half-life of orbifloxacin in plasma was 7.3 ± 1.1 hours for rabbits administered the 10 mg/kg dose and 8.6 ± 0.55 hours for rabbits administered the 20 mg/kg dose. Mean bioavailability was 52.5% for rabbits administered the 10 mg/kg dose and 46.5% for rabbits administered the 20 mg/kg dose.
CONCLUSIONS AND CLINICAL RELEVANCE Results provided pharmacokinetic properties for 2 doses (10 mg/kg and 20 mg/kg) of orbifloxacin oral suspension in rabbits. Further studies are necessary to determine the protein-binding activity of orbifloxacin in rabbits before dosages for the treatment of common pathogens in this species are recommended.
Abstract
OBJECTIVE To determine pharmacokinetic and pharmacodynamic properties of the novel factor Xa inhibitor apixaban in clinically normal cats.
ANIMALS 5 purpose-bred domestic shorthair cats.
PROCEDURES A single dose of apixaban (0.2 mg/kg, PO) was administered to each cat (time 0), and blood samples were obtained at 0, 15, 30, 45, 60, 120, 240, 360, 480, and 1,440 minutes. After a 1-week washout period, another dose of apixaban (0.2 mg/kg, IV) was administered to each cat, and blood samples were obtained at 0, 5, 10, 15, 30, 45, 60, 120, 240, 360, 480, and 1,440 minutes. Apixaban concentrations in plasma were measured via liquid chromatography–tandem mass spectrometry. Pharmacodynamic effects of apixaban were determined with a commercial assay for factor × activity, which measures endogenous factor Xa activity chromogenically.
RESULTS Factor Xa was inhibited as a function of time after a single dose of apixaban administered orally or IV, and a direct inverse correlation with the plasma apixaban concentration was detected. Pharmacokinetic analysis revealed moderate clearance, short half-life, and high bioavailability for apixaban. A 2-compartment model was fit to the IV pharmacokinetic data; compartmental modeling could not be used to adequately describe the oral data because of substantial interindividual variability.
CONCLUSIONS AND CLINICAL RELEVANCE Results inticated that apixaban was an effective inhibitor of factor Xa in cats. Further studies will be needed to determine pharmacokinetics and pharmacodynamics after multidose administration, effects of cardiac disease on pharmacokinetics and pharmacodynamics, dosing recommendations, and efficacy of apixaban for use in the treatment and prevention of thromboembolic disease in cats.
