Single-dose pharmacokinetics and cardiovascular effects of oral pimobendan in healthy cats

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• 作者：M. Yata ; BVSc (Hons)^a ; A.J. McLachlan ; BPharm (Hons) ; PhD^b ; D.J.R. Foster ; BSc (Hons) ; PhD^c ; ^d ; A.S. Hanzlicek ; MS ; DVM^e ; N.J. Beijerink ; DVM ; PhD^a ; ^{niek.beijerink@sydney.edu.au" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Metabolite pharmacokinetics ; UD-CG 212 ; Inodilator ; Feline ; Pharmacodynamics
• 刊名：Journal of Veterinary Cardiology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：18
• 期：4
• 页码：310-325
• 全文大小：938 K

文摘

To investigate the pharmacokinetics and pharmacodynamics of oral pimobendan in conscious, healthy cats.

Animals

Eight healthy adult cats.

Materials and methods

A randomised, single-blinded, crossover design was used. Two oral doses of pimobendan (0.625-mg [LD], 1.25-mg [HD]) and a control substance (3-mL water) were administered to each cat. Blood collection, echocardiography, and oscillometric blood pressure measurements were performed repeatedly for 12 h following each dose. Plasma concentrations of pimobendan and the active metabolite, O-desmethylpimobendan (ODMP), were quantified using ultra-high-performance liquid chromatography tandem mass spectrometry. Cardiovascular parameters were evaluated for between- and within-treatment effects over time using linear mixed modelling.

Results

Pimobendan was rapidly absorbed and converted to ODMP with the pimobendan AUC_0–∞ greater than ODMP AUC_0–∞ (ODMP:pimobendan AUC_0–∞ ratio 0.6 [LD] and 0.5 [HD]) despite a longer elimination half-life of ODMP (pimobendan t_1/2 0.8 h vs. ODMP t_1/2 1.6 h [LD]; pimobendan t_1/2 0.7 h vs. ODMP t_1/2 1.3 h [HD]). Averaged across all time points, pimobendan increased several measures of systolic function; however, its effect could not be further characterised. Although treatment was well-tolerated, two cats vomited following HD and another had a ventricular premature beat recorded following LD.

Conclusions

The lower ODMP:pimobendan AUC_0–∞ ratio compared to that observed previously in dogs suggests reduced metabolism in cats. Treatment effects were observed in measures of systolic function; however, the duration of action and differences in effects between the two pimobendan doses could not be characterised. Further studies are required to evaluate pimobendan in feline cardiovascular medicine.