Dose-response following single administrations of a new cardiac performance enhancer RO 13-6438 in normal volunteers.

Abstract

We assessed the changes in cardiovascular function in humans caused by RO 13-6438, a new drug that enhances cardiac performance, by means of noninvasive methods which included measurement of systolic time intervals and electrical impedance cardiography. Twelve healthy male volunteers received RO 13-6438 doses of 10 and 20 mg intravenously and 20, 40, and 60 mg orally according to a double blind, randomized, crossover, placebo-controlled design. A dose-dependent distinct enhancement in cardiac performance was seen. This was attributed to positive inotropism (shortening of heart rate-corrected electromechanical systole) and to a vasodilating action (decline of diastolic blood pressure and total peripheral resistance). In addition, the drug increased heart rate slightly. The cardiac effects were detectable for 6 h. To reach the average equivalent inotropic response over 6 h, the oral dose was approximately 1.8-fold of the i.v.; this indicated a high bioavailability of RO 13-6438. Transient color vision disturbances were reported mainly following the intravenous administration. The properties of RO 13-6438 suggests that it may be useful for treatment of heart failure.

• Authors: G G Belz, H C Stern, R Butzer
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) 1985 Jan-Feb Vol. 7 Issue 1 Pg. 86-90 ISSN: 0160-2446 [Print] United States
• PMID: 2580156 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)

Chemical References

• Cardiotonic Agents
• Quinazolines
• Vasodilator Agents
• quazinone

Topics

• Adult
• Blood Pressure (drug effects)
• Cardiac Output (drug effects)
• Cardiotonic Agents (pharmacology, toxicity)
• Dose-Response Relationship, Drug
• Heart Rate (drug effects)
• Humans
• Male
• Quinazolines (pharmacology, toxicity)
• Systole (drug effects)
• Vascular Resistance (drug effects)
• Vasodilator Agents (pharmacology, toxicity)