Summary
The pharmacokinetics of an i.v. bolus of pimobendan (P) 2.5 mg and 5.0 mg, its tolerability and the effect on heart rate and blood pressure have been studied in 12 subjects (42–70 y) suffering from severe terminal renal impairment. Plasma level data were compared with those obtained in a previous investigation in healthy volunteers. Pharmacokinetics were dose linear and were comparable to those in healthy subjects. No adjustment of the dose of P is necessary in patients with severe renal impairment. Tolerability of P, observed by means of blood pressure monitoring, clinical chemistry tests, electrocardiography and subjective judgement resulted in 4 complaints out of 12 patients: three suffered from orthostatic problems and vomiting, and one patient had nausea. Mean heart rate was elevated by 19% (2.5 mg) and 16% (5.0 mg). Blood pressure was significantly reduced after 2.5 mg P (23% systolic and 26% diastolic pressure), and after 5.0 mg P by 25% systolic and 23% diastolic pressure.
Similar content being viewed by others
References
Berger C, Meyer W, Scholz H, Starbatty J (1985) Effects of the benzimidazole derivatives pimobendan and 2-(4-hydroxyphenyl)-5-(5-methyl-3-oxo-4,5-dihydro-2H-6-pyridazinyl)-benzim idazole HCl on phosphodiesterase activity and force of contraction in guinea-pig hearts. Arzneimittelforschung 35: 1668–1673
Dämmgen J, Trach V (1988) Wirkung von Pimobendan (P) (UD-CG 115) auf das ischämische bzw. reperfundierte Myocard des narkotisierten Hundes. Z Kardiol 77 [Suppl 1]: 58
Rüegg JC, Pfitzer G, Eubler D, Zeugner C (1984) Effect on contractility of skinned fibers from mammalian heart and smooth muscle by a new benzimidazide derivative, 4,5-dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazole-5-yl]-5-methyl-3 (2H)-pyridazinone. Arzneimittelforschung 34: 1736–1738
Diederen W (1984) Improvement of ventricular function in dogs by the cardiotonic drug pimobendan in comparison to the vasodilators captopril and dihydralazine. Cell Calcium 5: 312
Verdouw PD, Hartog JM, Duncker DJ, Roth W, Saxena PR (1986) Cardiovascular profile of pimobendan, a phosphodiesterase inhibitor with vasodilator and inotropic properties. Eur J Pharmacol 126: 21–30
Duncker DJ, Dalen FJ van, Hartog JM, Lamers JMJ, Rensen RJ, Saxena PR, Verdouw PD (1986) Usefulness of pimobendan in the treatment of heart failure. Arzneimittelforschung 36: 1740–1744
Renard M, Walter M, Liebens I, Dresse A (1988) Pimobendan (UD-CG 115 BS) in chronic congestive heart failure. Chest 93: 1159–1164
Baumann G, Ningel K, Permanetter B (1989) Cardiovascular profile of UD-CG 115 BS (pimobendan) and reversibility of catecholamine subsensitivity in severe congestive heart failure secondary to idiopathic dilated cardiomyopathy. J Cardiovasc Pharmacol 13: 730–738
Pouleur H, Hanet C, Schröder E, Col J, Mechelen H van, Etienne J, Rousseau MF (1989) Effects of pimobendan (UD-CG 115 BS) on left ventricular inotropic state in conscious dogs and in patients with heart failure. J Cardiovasc Pharmacol 14 [Suppl]: 518–522
Roth W, Beschke K, Jauch R, Zimmer A, Koss FW (1981) Fully automated high-performance liquid chromatography. A new chromatograph for pharmacokinetic drug monitoring by direct injection of body fluids. J Chromatogr 222: 13–22
Bozler G (1977) Modellentwicklungen in der Pharmakokinetik. Arzneimittelforschung 27: 895–932
Yamaoka K, Nakagawa T, Uno T (1978) Application of Akaike's Information Criterion (AIC) in the Evaluation of Linear Pharmacokinetic Equations. J Pharmacokinet Biopharm 6: 165–175
Mertz DP (1980) Arzneimittelgabe bei Niereninsuffizienz. Med Klin 75: 564–569
Fabre J, Balant M (1983) Renal failure, drug pharmacokinetics and drug action in handbook of clinical pharmacokinetics. In: Gibaldi M, Prescott L (eds) ADIS Health Science Press, New York, pp 212–234
Bennett WM (1975) Principles of drug action in patients with renal disease. Western J Med 123: 372–379
Kitzen JM, Lynch JJ, Driscoll EM, Luccheri BR (1988) Cardiac electrophysiologic and hemodynamic activity of pimobendan (UD-CG 115 BS) a new inotropic agent. J Pharmacol Exp Ther 244: 929–939
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Przechera, M., Roth, W., Kühlkamp, V. et al. Pharmacokinetic profile and tolerability of pimobendan in patients with terminal renal insufficiency. Eur J Clin Pharmacol 40, 107–111 (1991). https://doi.org/10.1007/BF00315148
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00315148