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- Author or Editor: Max P. Maurer x
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Abstract
Objective—To determine pharmacokinetics of clomipramine and its principle metabolite (desmethylclomipramine) in the plasma of dogs after IV or oral administration of a single dose.
Animals—6 male and 6 female Beagles.
Procedures—Clomipramine was administered IV (2 mg/kg), PO (4 mg/kg) after food was withheld for 15 hours, and PO (4 mg/kg) within 25 minutes after dogs were fed. Plasma clomipramine and desmethylclomipramine concentrations were measured by use of a gas chromatography with mass-selection method.
Results—Time to peak plasma concentrations of clomipramine and desmethylclomipramine following oral administration was 1.2 hours. For clomipramine, after IV administration, elimination half-life was 5 hours, mean residence time was 3 hours, and plasma clearance was 1.4 L/h/kg. Values for mean residence time and terminal half-life following oral administration were similar to values obtained following IV administration, and systemic bioavailability was approximately 20% for clomipramine and 140% for desmethylclomipramine, indicating fast absorption of clomipramine from the gastrointestinal tract and extensive first-pass metabolism. Administration of clomipramine with food did not alter the area under the concentration versus time curve for desmethylclomipramine but resulted in a 25% increase for clomipramine. Clomipramine and desmethylclomipramine were extensively bound (> 96%) to serum proteins. There were no significant differences in area under the concentration versus time curve between male and female dogs.
Conclusions and Clinical Relevance—Results indicate that there should not be any clinically important differences in efficacy regardless of whether clomipramine is administered with or without food. (Am J Vet Res 2000;61:74–79)
Abstract
Objective—To determine pharmacokinetics of clomipramine and its principle metabolite (desmethylclomipramine) in the plasma of dogs following singledose and repeated-dose oral administration at various dosages.
Animals—9 male and 9 female Beagles.
Procedures—Clomipramine was administered orally at a dose of 1, 2, or 4 mg/kg to 3 male and 3 female dogs, first as a single dose and then, after an interval of 14 days, twice daily for 10 days. Plasma clomipramine and desmethylclomipramine concentrations were measured by use of a gas chromatography with mass-selection method.
Results—Dose-related accumulation was detected following repeated-dose administration. Accumulation ratios after administration of clomipramine at dosages of 1, 2, and 4 mg/kg twice daily were 1.4, 1.6, and 3.8, respectively, for clomipramine and 2.1, 3.7, and 7.6, respectively, for desmethylclomipramine. Terminal half-life increased slightly (1.6-fold for clomipramine and 1.2-fold for desmethylclomipramine) with repeated- dose administration but remained short in all groups (≤ 4 hours). Steady state was reached within 4 days in all animals. Ratios of the areas under the concentration versus time curves from time 0 to 12 hours for clomipramine and desmethylclomipramine were 3.9, 3.1, and 1.5 after repeated administration at dosages of 1, 2, and 4 mg/kg every 12 hours, respectively. Areas under the concentration versus time curve, mean residence times, and terminal half-lives were not significantly different between male and female dogs.
Conclusions and Clinical Relevance—Repeated administration of clomipramine results in higher concentrations of clomipramine than desmethylclomipramine in dogs. (Am J Vet Res 2000;61:80–85)
Abstract
Objective—To establish pharmacokinetics of robenacoxib after administration to cats via the IV, SC, and oral routes.
Animals—24 cats.
Procedures—In a crossover design, robenacoxib was administered IV, SC, and orally (experiment 1) and orally (experiment 2) to cats with different feeding regimens. Blood robenacoxib concentrations were assayed, with a lower limit of quantification of 3 ng/mL.
Results—In experiment 1, geometric mean pharmacokinetic values after IV administration of robenacoxib were as follows: blood clearance, 0.44 L/kg/h; plasma clearance, 0.29 L/kg/h; elimination half-life, 1.49 hours; and volume of distribution at steady state (determined from estimated plasma concentrations), 0.13 L/kg. Mean bioavailability was 69% and median time to maximum concentration (Cmax) was 1 hour for cats after SC administration of robenacoxib, whereas mean bioavailability was 49% and 10% and median time to Cmax was 1 hour and 30 minutes after oral administration to cats after food withholding and after cats were fed their entire ration, respectively. In experiment 2, geometric mean Cmax was 1,159, 1,201, and 692 ng/mL and area under the curve from 0 to infinity was 1,337, 1,383, and 1,069 ng × h/mL following oral administration to cats after food withholding, cats fed one-third of the daily ration, and cats fed the entire daily ration, respectively.
Conclusions and Clinical Relevance—For treatment of acute conditions in cats, it is recommended to administer robenacoxib by IV or SC injection, orally after food withholding, or orally with a small amount of food to obtain optimal bioavailability and Cmax.
