PHARMACOKINETIC BEHAVIOR AND CARDIOVASCULAR EFFECTS OF INTRAVENOUSLY ADMINISTERED HYPOXOSIDE AND ROOPEROL

This study concerns the pharmacokinetic behaviour and cardiovascular e ffects of rapid infusions of hypoxoside (GAS 83643-94-1) and rooperol (GAS 83644-00-2) in anaesthetised Chacma baboons. Institutional approv al was obtained and animal care conformed to international guidelines. Hypoxoside (500 mg) and rooperol (240 mg) dissolved in isotonic salin e were infused during 15 min. Concentration-time data from high perfor mance liquid chromatography of arterial blood samples were subjected t o non-linear curve-fitting to obtain two-compartment mammillary pharma cokinetic models. Mean values were: GRAPHICS Hypoxoside was eliminated without significant metabolite formation and it revealed no cardiovas cular effects. Rooperol was metabolized rapidly with formation of nine metabolites of which the major three were the diglucuronide, disulpha te and mixed glucuronide sulphate: Rooperol caused moderate, transient increased cardiac output, stroke volume and vascular pressures withou t increased heart rate or filling pressures, suggestive of increased m yocardial contractility probably allied to its catechol structure.