Pharmacokinetics of enoximone after various intravenous administrations to healthy volunteers.

The pharmacokinetics of enoximone and its sulfoxide metabolite were investigated in healthy male volunteers after various intravenous administrations: a bolus single dose, a continuous infusion, and bolus multiple doses of enoximone. The overall pharmacokinetic profiles of enoximone and sulfoxide metabolite indicated linearity over the range of 0.25-2.0 mg/kg after single doses of enoximone. The hypothetical plasma concentration just after bolus injection of enoximone, the maximum concentration of sulfoxide, and the area under the concentration-time curves of both compounds increased proportionally with dose. The terminal half-lives of both compounds indicated similar values (2.0-2.7 h) and were not dose related. After four consecutive doses given at 3-h intervals, no accumulation was observed for either compound, and the pharmacokinetic parameters were not altered. After a 4-h infusion of enoximone, the areas under the plasma concentration-time curves of both compounds were 30% lower than the estimated values from the single dose study. Also, some pharmacokinetic parameters were changed as compared to those from the single dose study. The pharmacokinetic parameters obtained in Japanese healthy volunteers showed no marked differences from those obtained in Caucasians; thus, no racial difference was suggested in the pharmacokinetic properties of enoximone.

Pharmacokinetics of probucol in male rats.

The bioavailability and pharmacokinetic behavior of 10 mg/kg of [14C]probucol in an oil-water emulsion was determined after oral and intravenous administration to rats. The bioavailability of the oral formulation was approximately 6%. For the first 12-h interval after the intravenous bolus, plasma probucol concentrations increased after an initial decrease. This effect may be attributed to the formulation or precipitation of the drug in the vasculature. The terminal plasma half-life was 6 d. By 7 d, 45 and 4.65% of the labeled intravenous bolus was excreted in the feces and in the urine, respectively. Although most of the labeled dose was excreted in the bile, any enterohepatic recirculation that did occur did not contribute to the atypical plasma concentration versus time profile. The tissue distribution of the label and elimination rates in the bile differed between the two routes of administration. Either the total body burden, precipitation of the drug, or the emulsion vehicle may be responsible for the nonlinear distribution and clearance of the intravenous dose.

[Plasma levels of probucol in man after single and repeated oral doses (author's transl)]. / Taux plasmatiques du probucol chez l'homme après administration orale unique ou répétée.

Following administration of a single oral dose of 3 g probucol to healthy volunteers, mean peak plasma concentrations of 3.9 microgram/ml were observed at 24 hours. Successive blood levels measurements showed diphasic elimination, with half-lives of about 1 and 23 days. Plasma levels after a single 250 mg dose in volunteers are also reported. In 51 patients who received probucol 1 g daily for periods of 1 to 12 months, a concentration plateau was obtained within 1 to 3 months of treatment; the mean plasma levels ranged from 18.2 to 39.2 microgram/ml depending on the duration of probucol therapy. In another study carried out on 8 patients who were given the same daily dose during 12 months, the mean probucol plasma level at the end of that period was 18.9 microgram/ml. Repeated administration of probucol to healthy volunteers showed good correlation between dosage and blood levels.

Absorption, distribution, and excretion of 14C-meglumine in rats and dogs after administration of 14C-meglumine salicylate.

Meglumine labeled with carbon-14 was administered orally as 14C-meglumine salicylate to rats and dogs to study its distribution and excretion. The compound was incompletely absorbed; that which was absorbed was rapidly excreted in the urine. Peak blood levels were about 5-10 mug/ml in rats and 2-8 mug/ml in dogs. Tissue levels were negligible at the end of the experimental periods. No evidence for N-demethylation or oxidation to carbon dioxide was obtained.