Abstract
The pharmacokinetics of piroximone (PI) were determined in patients with renal failure (inulin clearance less than 50 ml min-1 per 1.73 m2) using two protocols: (a) 10 patients received a single i.v. infusion of 0.5 mg kg-1 PI and the data were compared with those from seven healthy subjects receiving the same regimen; (b), a single oral dose of either 25 or 50 mg PI was given to 20 patients. PI concentrations were assayed by h.p.l.c. in plasma and urine over 48 h. After i.v. administration to healthy subjects PI was distributed rapidly and eliminated with a mean half-life of 1.3 +/- 0.2 h. The urinary recovery of unchanged PI was 64% of the dose. In the patients the extent of renal elimination of PI was decreased (-78%) in relation to the degree of renal insufficiency as assessed by inulin clearance (r = 0.97, P < 0.0001). Mean Cmax, AUC and t1/2,z values after i.v. infusion were increased by 47%, 127% and 77%, respectively, in comparison with healthy subjects. Similar results were obtained after oral administration. Until chronic dosing studies are undertaken, PI dosage should be adapted in relation to renal function.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Colucci W. S., Wright R. F., Braunwald E. New positive inotropic agents in the treatment of congestive heart failure. Mechanisms of action and recent clinical developments. 2. N Engl J Med. 1986 Feb 6;314(6):349–358. doi: 10.1056/NEJM198602063140605. [DOI] [PubMed] [Google Scholar]
- Haegele K. D., Belz G. G., Meinicke T. T., Schechter P. J. Pharmacokinetics of piroximone (MDL 19.205) in healthy volunteers. Eur J Clin Pharmacol. 1986;31(2):239–242. doi: 10.1007/BF00606667. [DOI] [PubMed] [Google Scholar]
- Haegele K. D., Hinze C., Joder-Ohlenbusch A. M., Cremer G., Borlak J. Effects of a standardized meal on the pharmacokinetics of the new cardiotonic agent piroximone. Arzneimittelforschung. 1991 Dec;41(12):1225–1229. [PubMed] [Google Scholar]
- Petein M., Levine T. B., Cohn J. N. Hemodynamic effects of a new inotropic agent, piroximone (MDL 19205), in patients with chronic heart failure. J Am Coll Cardiol. 1984 Aug;4(2):364–371. doi: 10.1016/s0735-1097(84)80227-2. [DOI] [PubMed] [Google Scholar]