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Abstract

Objective—To validate use of high-performance liquid chromatography (HPLC) in determining imipramine concentrations in equine serum and to determine pharmacokinetics of imipramine in narcoleptic horses.

Animals—5 horses with adult-onset narcolepsy.

Procedure—Blood samples were collected before (time 0) and 3, 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 3, 4, 6, 8, 12, and 24 hours after IV administration of imipramine hydrochloride (2 or 4 mg/kg of body weight). Serum was analyzed, using HPLC, to determine imipramine concentration. The serum concentration-versus-time curve for each horse was analyzed separately to estimate pharmacokinetic values.

Results—Adverse effects (muscle fasciculations, tachycardia, hyperresponsiveness to sound, and hemolysis) were detected in most horses when serum imipramine concentrations were high, and these effects were most severe in horses receiving 4 mg of imipramine/kg. Residual adverse effects were not apparent. Value (mean ± SD) for area under the curve was 3.9 ± 0.7 h × μg/ml, whereas volume of distribution was 584 ± 161.7 ml/kg, total body clearance was 522 ± 102 ml/kg/h, and mean residence time was 1.8 ± 0.6 hours. One horse had signs of narcolepsy 6 and 12 hours after imipramine administration; corrresponding serum imipramine concentrations were less than the therapeutic range.

Conclusions and Clinical Relevance—Potentially serious adverse effects may be seen in horses administered doses of imipramine that exceed a dosage of 2 mg/kg. Total body clearance of imipramine in horses is slower than that in humans; thus, the interval between subsequent doses should be longer in horses. (Am J Vet Res 2001;62:783–786)

Full access
in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine whether the reported drug-drug interaction between the flea medication spinosad and ivermectin is attributable to inhibition of P-glycoprotein by spinosad.

Animals—6 healthy adult dogs with the ABCB1 wildtype genotype.

Procedures—The study was conducted as a prospective, masked, randomized crossover design. Six dogs were allocated to 2 groups; each dog served as its own control animal. Dogs in one of the groups received spinosad at the manufacturer's recommended dose; the other group received no treatment. Forty-eight hours later, scintigraphic imaging of the head and abdomen were performed with the radiolabeled P-glycoprotein substrate methoxy-isobutyl-isonitrile (sestamibi) in both groups of dogs. After a washout period of 60 days, the dogs in each group received the alternate treatment, and scintigraphic imaging again was performed 48 hours later. Gallbladder-to-liver and brain-to-neck musculature ratios of technetium Tc 99m sestamibi were calculated for each dog and compared between treatments.

Results—No significant differences in gallbladder-to-liver or brain-to-neck musculature ratios were found between treatments.

Conclusions and Clinical Relevance—Results provided evidence that spinosad did not inhibit P-glycoprotein function 48 hours after spinosad was administered at the manufacturer's recommended dose. Further investigations will be necessary to elucidate the mechanism of the reported toxic interaction between spinosad and ivermectin.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the pharmacokinetics of gallium maltolate (GaM) after intragastric administration in healthy foals.

Animals—6 healthy neonatal foals.

Procedures—Each foal received GaM (20 mg/kg) by intragastric administration. Blood samples were obtained before (time 0) and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, and 48 hours after GaM administration for determination of serum gallium concentrations by use of inductively coupled plasma mass spectroscopy.

Results—Mean ± SD pharmacokinetic variables were as follows: peak serum gallium concentration, 1,079 ± 311 ng/mL; time to peak serum concentration, 4.3 ± 2.0 hours; area under the serum concentration versus time curve, 40,215 ± 8,420 ng/mL/h; mean residence time, 39.5 ± 17.2 hours; area under the moment curve, 1,636,554 ± 931,458 ng([h]2/mL); and terminal half-life, 26.6 ± 11.6 hours. The mean serum concentration of gallium at 12 hours was 756 ± 195 ng/mL.

Conclusions and Clinical Relevance—Gallium maltolate administered via nasogastric tube at a dose of 20 mg/kg to neonatal foals resulted in gallium serum concentrations considered sufficient to suppress growth or kill Rhodococcus equi in macrophages and other infected tissues.

Full access
in American Journal of Veterinary Research