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The oral pharmacokinetics of aminoglutethimide were determined in 17 patients receiving the drug therapeutically. The absorption of aminoglutethimide after oral intake was almost complete as judged by recovery of radio-labelled drug in the urine. The plasma half-life of the drug was markedly reduced (mean 43%) during multiple-dose administration as compared with a single dose, but only a moderate increase in total clearance (mean 26.9%) was observed. This finding was consistent with a significant reduction (mean 29.2%) in apparent volume of distribution (Vd) occurring during prolonged treatment. These alterations in drug distribution could also be demonstrated after a drug-free interval of 96 hours during treatment. The reduction in apparent volume of distribution could not be explained by altered plasma protein binding of aminoglutethimide, as evaluated by equilibrium dialysis experiments.

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