A method based on reverse extraction and thin-layer chromatography has been developed for the isolation and quantitative determination of 2β,16β-bis-[4'-methyl-(4'-14C)methyl-piperazino]-3α,17β-diacetoxy-5α-androstane dibromide (pipecurium bromide, RGH-1106, Arduan) from biological fluids. The procedure appeared to be suitable also for the separation of the steroid itself and its deacetylated metabolites. Pharmacokinetics of pipecurium bromide was studied by a two-compartment analysis of plasma disappearance curves following a single i.v. injection of 14C-labelled compound to rats. According to the observations, the biological half-life of the compound averaged 41 min. The V1 and V2 values around 130 ml revealed virtual inner and outer distribution volumes. The small rate constants (0.02 for K1 and 0.05 for K2, as a mean) showed a poor binding to plasma proteins and a rapid transfer of the drug between the two compartments. A metabolic clearance pattern of 9.6 ml/min was observed. The rate of hepatic elimination of the compound and/or its metabolites reached 6% after 4 h. Thin-layer chromatographic separation and tentative identification of metabolites showed the free dihydroxymetabolite and suggested a monoacetate to be present in plasma and bile.
|Number of pages||5|
|Issue number||2 A|
|Publication status||Published - Jan 1 1980|
ASJC Scopus subject areas
- Drug Discovery