Pharmacokinetics of oral pimobendan in healthy cats

Objective: To describe the pharmacokinetics of oral pimobendan in healthy cats. Animals: 18 purpose-bred cats. Methods: In 10 cats, blood samples were collected before, and at multiple time points after, a single oral dose of pimobendan (0.28 +/- 0.04 mg/kg). In 8 cats, blood samples were collected at 3 various time points on the first and third days of twice daily oral dosing of pimobendan for a total of 7 doses (0.31 +/- 0.04 mg/kg). Plasma concentrations. of pimobendan were quantified by high pressure liquid chromatography coupled to tandem mass spectrometry. Results: A 1-compartment open model with first order absorption in and elimination from the central compartment with a lag time best describes the disposition of pimobendan. Two cats were removed from final pharmacokinetic descriptive analysis due to delayed minimal absorption from gastrointestinal adverse effects. After a lag time (0.3 +/- 0.06 h), pimobendan was rapidly absorbed (absorption half-life- = 0.2 +/- 0.08 h) and eliminated (elimination half-life = 1.3 +/- 0.2 h). Maximum plasma concentrations (34.50 +/- 6.59 ng/mL) were high and were predicted 0.9 h after drug administration. Apparent volume of distribution at steady state (per bioavailability) was large (8.2 +/- 2.5 L/kg). The multi-dose study showed the pharmacokinetic model to be robust. Conclusion: When administered a similar dose on a per weight basis, pimobendan has a substantially longer elimination half-life and maximal drug plasma concentration in cats as compared to those previously reported in dogs. (C) 2012 Elsevier B.V. All rights reserved.