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

Abstract

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, and t _1/2 was 5.0 ± 2.7 vs. 8.3 ± 4.8, with AUC of 167.8 ± 36.2 vs. 50.1 ± 19.2 and F of 28 ± 6. The differences between PO and PR were significant (P < 0.03) for AUC and C _max for both PIM and ODMP. Conclusions and Clinical Relevance: The pharmacokinetics of PIM and ODMP were described following PO and PR administration. The 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 and which are unable to receive medication PO.

Keywords: bioavailability; congestive heart failure; pharmacokinetics; pimobendan; rectal drug administration.

Figure 1

Mean ± SD of concentration–time plots of PIM and ODMP for dogs treated with a single dose of 0.5 mg/kg pimobendan per os (n = 7) vs. per rectum (n = 8). ODMP, o-desmethyl-pimobendan; PIM, pimobendan.