The pharmacokinetics of Casodex in prostate cancer patients after single and during multiple dosing

European Urology
I D CockshottL Denis

Abstract

The pharmacokinetics of Casodex have been investigated in patients with prostatic carcinoma following single oral doses of 10 mg, 30 mg and 50 mg and during daily administration at these dose levels. Casodex displays prolonged absorption following a single dose, with peak plasma concentrations observed at up to 8 h for doses of 10 mg and 30 mg and up to 48 h for the 50 mg dose. The area under the plasma concentration-time curve increased linearly with dose, and Casodex was eliminated slowly from plasma (t1/2 about 6 days). During daily administration, Casodex accumulates about 10-fold in plasma at all dose levels; this is consistent with its long plasma elimination half-life, estimated by curve fitting of these multiple dose data to be 7-10 days. Trough plasma concentrations increased linearly with dose after both single and multiple dosing, achieving mean values of 1.80, 6.89 and 9.33 micrograms/ml for the 10 mg, 30 mg and 50 mg dose levels, respectively, after 12 weeks' dosing. Neither efficiency of renal function nor age had any apparent effect on the pharmacokinetics of Casodex. The pharmacokinetics of Casodex make it ideally suited to once-daily administration.

Citations

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