The effect of excipients on the oral absorption of pimobendan in healthy dogs

Compounded pimobendan is prescribed without knowledge of the effect of excipients. The objective of this study was to test the effect of certain excipients on oral absorption in dogs by describing the single-dose pharmacokinetics of pimobendan and its active metabolite (o-desmethyl-pimobendan [ODMP]) following oral administration of two experimental pimobendan formulations, and to compare these pharmacokinetic estimates to those of an FDA-approved product (Vetmedin®).

Seven healthy adult purpose-bred dogs

Dogs were administered 2.5 mg of pimobendan as a single oral dose of Vetmedin®, or of an experimental capsule with or without citrate as an excipient, in a randomized, prospective cross-over study with a two-week washout period between treatments. Blood samples were obtained at pre-determined timepoints before and for 24 hours post-dose for quantification of pimobendan and ODMP using ultra-high-pressure liquid chromatography with mass spectrometry. Compartmental analysis was used to obtain pharmacokinetic parameters. Data are presented as geometric mean (CV%).

Peak plasma pimobendan concentrations (C_MAX) were 8.82 ng/mL (53%), 5.85 ng/mL(76%), and 8.11 ng/mL (70%), and areas under the concentration-time curve (AUC) were 19.0 hr*ng/mL (55%), 13.6 hr*ng/mL (68%) and 19.7 hr*ng/mL (40%) for Vetmedin®, citrate-containing capsules and citrate-free capsules, respectively. Experimental formulations had high relative absorption (AUC_{(test drug)}/AUC_(Vetmedin®), 72% [61%] and 103% [71%] for citrate-containing and citrate free-capsules, respectively). There was moderate-to-high inter-individual pharmacokinetic variability for all formulations. No differences in C_MAX or AUC were found among treatments.

Small sample size