Abstract
Summary
The action of methandrostenolone on phenylbutazone and its major metabolite, oxyphenbutazone, has been studied in man by determining the half-life and plateau plasma levels of the antirheumatic drugs. The anabolic steroid caused an increase in the plasma level of oxyphenbutazone, confirming previous studies. This effect was previously attributed to a change in volume of distribution. In the present study, in addition to the effect on volume of distribution, a prolongation of half-life of oxyphenbutazone was observed in one subject. In contrast, in six patients receiving continuous therapy with phenylbutazone, plasma levels were unchanged when methandrostenolone was superimposed. The plasma levels of oxyphenbutazone, determined in the same samples, were unaffected. The half-life of phenylbutazone in two patients was not changed upon the administration of methandrostenolone, showing that no alteration had occurred in the metabolism of phenylbutazone. Equilibrium dialysis experiments indicated competition between phenylbutazone and oxyphenbutazone, and that the former has a relatively greater affinity for albumin. These findings suggest that phenylbutazone masks the influence of methadrostenolone on plasma levels of oxyphenbutazone, presumably by displacing oxyphenbutazone from plasma protein binding sites. Comparable in vitro studies with phenobarbital and p-hydroxyphenobarbital indicate the absence of significant competition for albumin binding sites.
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