proscillaridin and meproscillarin

Topics: Biological Availability; Digitalis Glycosides; Digitoxin; Digoxin; Drug Interactions; Half-Life; Humans; Intestinal Absorption; Kidney; Kinetics; Plants, Medicinal; Proscillaridin; Protein Binding; Serum Albumin

A placebo-controlled double-blind trial was conducted, to determine the onset of effect of Meproscillarin (injected intravenously). 28 days apart six healthy volunteers were given double-blind 1,0 mg Meproscillarin or placebo and 60 days later 0,6 mg Digoxin, each drug as short infusion over four minutes. The total electromechanical systole corrected for heart rate (QS2c), was used as criterion of the inotropic effect of the glycoside. After placebo there no changes were observed over a period of two hours. Both glycosides shortened QS2c for about--16 ms. From Meproscillarin a 40% higher dosis was required, to achieve the same effect as with digoxin. After use of Meproscillarin the peak effect was reached after ten minutes; after digoxin a period of 60--120 minutes were required. The results show that intravenously given Meproscillarin is a fast acting glycoside.

Topics: Adult; Bufanolides; Clinical Trials as Topic; Digoxin; Double-Blind Method; Female; Humans; Injections, Intravenous; Male; Myocardial Contraction; Placebos; Proscillaridin; Stimulation, Chemical; Time Factors

During a one week period patients with liver cirrhosis and a control group were treated with a repeated dosage of the new heart glcoside Meproscillarin. After achieving a steady state in plasma level the same Meproscillarin plasma levels were found among both groups. Compared with the control group no difference was detected in the elimination rate of Meproscillarin in patients with liver cirrhosis, which means a complex disturbed liver function. Nevertheless the greater variance of the Meproscillarin plasma levels in the patients with liver cirrhosis in comparison with the controls means a diminished predictability of the therapeutic success in the cirrhosis group. With this limitation Meproscillarin can be used therapeutically in patients with liver cirrhosis, because a toxic accumulation is not to be expected.

Topics: Adult; Aged; Bufanolides; Female; Half-Life; Humans; Liver Cirrhosis; Male; Middle Aged; Proscillaridin; Serum Albumin

Meproscillarin is a glycoside with a high bioavailability (about 70%) and an elimination independent of the renal function. It was to be investigated whether a good cardiac effectiveness can be demonstrated during oral long-term application of meproscillarin to patients with renal failure. 29 patients with renal failure of varying degree and concomitant heart failure were daily given an oral dose of 0.75 mg of meproscillarin over 14 days. The effectiveness of the glycoside was measured as change of the electromechanical systole (QS2c) and the quotient of the diameter of heart and thorax (C/T) from the 1st--15th day. The plasma levels of the glycoside were determined on the 1st, 8th, and 15th day. There was a significant shortening of QS2c (by mean = 27 ms, P less than 0.005) and a marked decrease in the size of the heart (P less than 0.0025); heart rate and PQ-interval were only insignificantly influenced. Plasma levels of 0.95 ng/ml were found after 8 days of treatment compared to 1.25 ng/ml after 15 days. As the pharmacokinetics of the glycoside is practically not influenced by the renal function, meproscillarin represents an alternative in the treatment of patients with heart failure and impaired renal function.

Topics: Adult; Aged; Bufanolides; Cardiac Volume; Drug Evaluation; Female; Heart Failure; Heart Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Proscillaridin