Pharmacokinetics and pharmacodynamics of methyl proscillaridin in healthy man

• Published in: European journal of clinical pharmacology 1976-06, Vol.10 (2), p.101-108
• Main Authors: Belz, G G, Schreiter, H, Wolf, G K
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Biological Availability; Bufanolides - analogs & derivatives; Clinical Trials as Topic; Half-Life; Humans; Infusions, Parenteral; Kinetics; Male; Proscillaridin - analogs & derivatives; Proscillaridin - blood; Proscillaridin - pharmacology; Radioactive Tracers; Rubidium
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/BF00609467

The aim of this study was to obtain data about the pharmacological properties of a new glycoside derivative in man. Plasma concentrations and ECG parameters were measured after oral and intravenous administration of a single dose of 1.2 mg methyl proscillaridin in 16 healthy volunteers, using a strictly randomized, two-period change-over design. Glycoside concentrations were measured using a modified 86Rb-erythrocyte-assay. QT-duration, corrected for frequency (QTc), was the principal variable measured in the ECG. By either route, there was a maximum plasma level after 1 hour, which had decreased to a minimum at 3 hours, followed by a second peak at 4 to 10 hours (orally greater than iv). From 10 to 72 hours the concentrations decreased with a median t 1/2 of 23.3 hours (iv) and 33.0 hours (orally). Comparison of the ratio of plasma concentrations following oral and iv administration resulted in a bioavailability of 69% using the 48 hour plasma levels, and 59% using the areas under the concentration-time curves. The mean QTc was maximally shortened to 28 msec at 1 hour after iv and to 19 msec at 10 hours after the oral dose. A distinct similarity between time-concentration and time-QTc curves was seen after the initial distribution phase, both after oral and intravenous administration. The new derivative shows a rapid elimination. Its bioavailability is reasonably high.