The pharmacokinetics of ketoconazole after chronic administration in adults

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Abstract
We have studied the pharmacokinetics of the anti-mycotic ketoconazole in seven patients who took it for 1–6 months at a dose of 200 mg daily. The mean elimination half-life of the drug was 3.3 h, and although the ketoconazole was given only once daily, a satisfactory clinical response was obtained in all seven individuals. Only a small fraction of the absorbed drug (mean 0.22%) was excreted unchanged in the urine, suggesting almost complete metabolism. Our results support the concept that anti-mycotic activity in the tissues continues after the plasma drug concentration has fallen below a critical level. Our results also support the concept of a change in pharmacokinetics with chronic dosing.

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