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1.
J Am Vet Med Assoc ; 250(5): 530-533, 2017 Mar 01.
Article in English | MEDLINE | ID: mdl-28207313

ABSTRACT

CASE DESCRIPTION A 6-year-old castrated male Boxer was evaluated for a 5-week history of frequent vomiting, melena, and signs of abdominal pain following accidental ingestion of 5 to ten 15-mg meloxicam tablets (approx ingested dose, 3.1 to 6.2 mg/kg [1.4 to 2.8 mg/lb]). CLINICAL FINDINGS Clinical signs persisted despite 3 weeks of treatment with sucralfate (41.8 mg/kg [19 mg/lb], PO, q 8 h) and omeprazole (0.8 mg/kg [0.36 mg/lb], PO, q 24 h). Results of a CBC and serum biochemical analysis were unremarkable. Abdominal ultrasonography revealed peptic ulceration, and esophagogastroduodenoscopy confirmed the presence of severe proximal duodenal ulceration. TREATMENT AND OUTCOME A radiotelemetric pH-monitoring capsule was placed in the gastric fundus under endoscopic guidance for continuous at-home monitoring of intragastric pH and response to treatment. Treatment was continued with sucralfate (as previously prescribed) and omeprazole at an increased administration frequency (0.8 mg/kg, PO, q 12 h). Intragastric pH was consistently ≥ 3.0 for > 75% of the day during treatment, with the exception of 1 day when a single dose of omeprazole was inadvertently missed. Ulceration and clinical signs completely resolved. CLINICAL RELEVANCE Continuous radiotelemetric monitoring of intragastric pH in the dog of this report was useful for confirming that treatment achieved a predetermined target pH and for demonstrating the impact of missed doses. Duodenal ulceration resolved with twice-daily but not once-daily omeprazole administration. Findings suggested that twice-daily administration of omeprazole may be necessary to achieve this target pH and that a pH ≥ 3.0 for 75% of the day may promote healing of peptic ulcers in dogs.


Subject(s)
Dog Diseases/pathology , Monitoring, Physiologic/veterinary , Peptic Ulcer/veterinary , Telemetry/veterinary , Animals , Anti-Ulcer Agents/administration & dosage , Anti-Ulcer Agents/therapeutic use , Dogs , Drug Therapy, Combination/veterinary , Hydrogen-Ion Concentration , Male , Monitoring, Physiologic/instrumentation , Monitoring, Physiologic/methods , Omeprazole/administration & dosage , Omeprazole/therapeutic use , Peptic Ulcer/diagnosis , Peptic Ulcer/drug therapy , Peptic Ulcer/pathology , Sucralfate/administration & dosage , Sucralfate/therapeutic use , Telemetry/instrumentation
2.
Am J Vet Res ; 77(1): 65-71, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26709938

ABSTRACT

OBJECTIVE: To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. ANIMALS: 5 healthy purpose-bred hounds. PROCEDURES: The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received rapamycin (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and noncompartmental analyses. RESULTS: Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in nanograms per milliliter. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, need to be determined.


Subject(s)
Dogs/blood , Sirolimus/pharmacokinetics , Administration, Oral , Animals , Area Under Curve , Chromatography, Liquid/methods , Half-Life
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