Metabolism and pharmacokinetics of the cardiotonic agent piroximone and of its major metabolite in dog

Article abstract of DOI:10.3109/00498259509061833

1. Piroximone was administered orally (p.o.) and intravenously (i.v.) to male Beagle dog. In vitro, piroximone was incubated with dog liver microsomes. 2. Piroximone was metabolized in vivo to five metabolites (1-5) representing approximately 20% of the total administered dose. 3. The parent drug and its metabolites were totally eliminated in urine. 4. Reduced piroximone (piroximole), representing approximately 10% of the administered dose, was identified as the major metabolic product in vivo. 5. In vitro, piroximone was metabolized by dog liver microsomes to isonicotinic acid (I) and piroximole (4), with the same ratio as in vivo (1:4 = 0.2). The Michaelis-Menten parameters were determined for piroximole formation and were: K(m app) = 733 μM and V(max app) = 232 pmol/mg protein/min. 6. Comparison of the pharmacokinetics of piroximone and piroximole revealed that both compounds were very well absorbed (F = 93 ± 7 and 89 ± 8% respectively), slightly distributed (V(d app) 0.78 ± 0.4 and 1.02 ± 0.09 l/kg p.o., and 0.95 ± 0.05 and 0.76 ± 0.13 l/kg i.v. respectively) and excreted into urine to the same extent (U(Ex) = 54.7 ± 1.2 and 53.2 ± 12.6% p.o., and 59.1 ± 5.3 and 51.2 ± 5.7% i.v. respectively), except that the clearance of piroximone was two-fold higher than that observed for piroximole (Cl(T) = 7.77 ± 1.35 and 4.12 ± 0.44 ml/min/kg p.o., and 7.68 ± 1.25 and 4.06 ± 0.51 ml/min/kg i.v, respectively).

Full text of DOI:10.3109/00498259509061833

Xenobiotica
the fate of foreign compounds in biological systems
ISSN: 0049-8254 (Print) 1366-5928 (Online) Journal homepage: http://www.tandfonline.com/loi/ixen20
Metabolism and pharmacokinetics of the
cardiotonic agent piroximone and of its major
metabolite in dog
M. Berg-Candolfi, B. Dulery, F. Jehl & K. D. Haegele
To cite this article: M. Berg-Candolfi, B. Dulery, F. Jehl & K. D. Haegele (1995) Metabolism and
pharmacokinetics of the cardiotonic agent piroximone and of its major metabolite in dog,
Xenobiotica, 25:1, 59-70, DOI: 10.3109/00498259509061833
To link to this article: http://dx.doi.org/10.3109/00498259509061833
Published online: 22 Sep 2008.
Submit your article to this journal
Article views: 6
View related articles
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=ixen20
Download by: [McMaster University]
Date: 18 April 2016, At: 15:41