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Pharmacokinetics of pimobendan and its metabolite o-desmethyl-pimobendan following rectal administration to healthy dogs


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dc.contributor.advisorKuo, Kendon
dc.contributor.authorHer, Jiwoong
dc.date.accessioned2020-06-29T18:25:33Z
dc.date.available2020-06-29T18:25:33Z
dc.date.issued2020-06-29
dc.identifier.urihttp://hdl.handle.net/10415/7255
dc.description.abstractPimobendan, a benzimidazole-pyridazinone derivative, is an inodilator that is used for the treatment of congestive heart failure in dogs. Pharmacokinetics of pimobendan and its active metabolite o-desmethyl pimobendan (ODMP) were prospectively characterized in eight healthy dogs using a randomized, crossover design with a 24-h washout after a single dose of pimobendan (0.5 mg/kg) administered either per rectum (PR) or per os (PO). Plasma PIM and ODMP were quantitated using high performance liquid chromatography using an assay validated in dogs. Data were subjected to non-compartmental analysis. Pimobendan PR was more rapidly absorbed [time to maximum concentration (Tmax) 1 ± 0.4 h] than PO (2.1 ± 0.9 h). Pimobendan was rapidly converted to ODMP within minutes after both PO and PR administrations. Plasma PIM and ODMP concentrations from pimobendan PR were found to be comparatively low at all time points compared to pimobendan PO. Pimobendan PR resulted in significantly lower Cmax (PIM 10.1 ± 2 ng/mL, ODMP 8.8 ± 4.8 ng/mL) than pimobendan PO (PIM 49.1 ± 28.7 ng/mL, ODMP 30.9 ± 10.4 ng/mL). Relative bioavailability (%) of PIM and ODMP after rectal dosing was 25 ± 8 and 28 ± 6, respectively. Pimobendan PR was well tolerated by study dogs. Findings suggest that pimobendan PR might achieve effective concentrations and as such warrant future studies of clinical effectiveness in treating dogs with congestive heart failure who are unable to receive medication PO.en_US
dc.rightsEMBARGO_GLOBALen_US
dc.subjectGeneral Veterinary Medicineen_US
dc.titlePharmacokinetics of pimobendan and its metabolite o-desmethyl-pimobendan following rectal administration to healthy dogsen_US
dc.typeMaster's Thesisen_US
dc.embargo.lengthMONTHS_WITHHELD:6en_US
dc.embargo.statusEMBARGOEDen_US
dc.embargo.enddate2020-12-28en_US
dc.contributor.committeeBacek, Lenore
dc.contributor.committeeWinter, Randolph
dc.contributor.committeeBoothe, Dawn
dc.creator.orcidhttps://orcid.org/0000-0003-3150-591Xen_US

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