Pharmacokinetics of Pimobendan and Its Metabolite O-Desmethyl-Pimobendan Following Rectal Administration to Healthy Dogs.

Objective:This study describes the pharmacokinetics of parent pimobendan (PIM) and its active metabolite, o-desmethyl-pimobendan (ODMP), after oral and rectal administration of pimobendan to healthy dogs. Animals:A total of eight healthy privately owned dogs were used in this study. Procedures:The dogs received a single dose (0.5 mg/kg) of a commercially available pimobendan tablet per os (PO). Twelve blood samples were collected over a 12-h period for pharmacokinetic analysis. After a 24-h washout period, the dogs received the same dose of pimobendan solution per rectum (PR), and samples were obtained at the same time for analysis. Results:For PIM, PO vs. PR, respectively, the mean maximum plasma concentration (C-max, ng/ml) was 49.1 +/- 28.7 vs. 10.1 +/- 2, the time to reach a maximum concentration (T-max, h) was 2.1 +/- 0.9 vs. 1 +/- 0.4, the disappearance half-life (t(1/2), h) was 1.8 +/- 0.8 vs. 2.2 +/- 0.6, and the area under the concentration-time curve (AUC, ng*h/ml) was 148.4 +/- 71.6 vs. 31.1 +/- 11.9, with relative bioavailability (F, %) of 25 +/- 8. For ODMP, PO vs. PR, respectively,C(max)was 30.9 +/- 10.4 vs. 8.8 +/- 4.8,T(max)was 3.2 +/- 1.6 vs. 1.7 +/- 1.1, andt(1/2)was 5.0 +/- 2.7 vs. 8.3 +/- 4.8, with AUC of 167.8 +/- 36.2 vs. 50.1 +/- 19.2 andFof 28 +/- 6. The differences between PO and PR were significant (P< 0.03) for AUC andC(max)for both PIM and ODMP.