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| Title: Pharmacodynamics and pharmacokinetics of bicalutamide:
defining an active dosing regimen. |
| Title Abreviation: Urology |
Date of Pub: 1996 Jan |
| Author: Denis L; Mahler C; |
| Issue/Part/Supplement: 1A Suppl |
Volume Issue: 47 |
Pagination: 26-8; discussion 29-32 |
| MESH Headings: Androgen Antagonists (*PK/TU); Anilides (*PK/TU);
Animal; Human; Male; Prostatic Neoplasms (DT); Support, Non-U.S. Gov't; -RN-; |
| Journal Title Code: WSY |
Publication Type: JOURNAL ARTICLE |
| Date of Entry: 960226N |
Entry Month: 9605 |
| Country: UNITED STATES |
Index Priority: 2 |
| Language: Eng |
Unique Identifier: 96149763 |
| Unique Identifier: 96149763 |
ISSN: 0090-4295 |
| Abstract: Bicalutamide, a potent nonsteroidal antiandrogenic
drug devoid of hormonal agonist activity, is considered to be a pure antiandrogen. Binding
of bicalutamide to the androgen receptor results in regression of prostate tumors.
The antiandrogenic activity resides exclusively in the R-enantiomer. The S-enantiomer of bicalutamide
is rapidly cleared, but the R-enantiomer has a plasma elimination half-life of about 1
week, with a tenfold plasma accumulation at all dose levels, making it suitable for a
once-daily administration. It has been shown that plasma concentrations increase linearly
with dose after either single or multiple dosing. These pharmacokinetics are not affected
by age, impairment of renal function, or mild-to-moderate hepatic impairment. Following
daily administration of single doses of 50 mg/day for 12 weeks result in steady-state
plasma concentrations for the R-enantiomer of +/- 9 micrograms/mL. A single dose of 50
mg/day was preferred because this dose resulted in a 50% decrease of prostatic acid
phosphate (PAP) in 83% of the treated patients. Subsequent studies focused on the decrease
of prostate-specific antigen (PSA) as a surrogate endpoint. Decreases of PSA of > or =
90% were noted with daily doses of 100-200 mg. The excellent safety profile allows further
investigations of doses up to 450 mg daily. Studies are ongoing to establish the most
efficient dose with acceptable levels of toxicity in order to maximize the effect of bicalutamide
on clinical response, time to progression, mortality, and quality of life. |
| Abstract By: Author |
| Address: Oncologic Centre, Antwerp, Belgium. |
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