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Prediction of alpha1-adrenoceptor occupancy in the human prostate from plasma concentrations of silodosin, tamsulosin and terazosin to treat urinary obstruction in benign prostatic hyperplasia.
Biol Pharm Bull. 2007 Jul; 30(7):1237-41.BP

Abstract

Alpha1-adrenoceptor antagonists are clinically useful for the improvement of urinary obstruction due to benign prostatic hyperplasia (BPH), and their therapeutic effects are mediated through the blockade of prostatic alpha(1)-adrenoceptors. The present study was undertaken to predict the magnitude and duration of alpha(1)-adrenoceptor occupancy in the human prostate after oral alpha(1)-adrenoceptor antagonists. Prostatic alpha(1)-adrenoceptor-binding parameters of silodosin were estimated by measuring specific [(3)H]prazosin binding in rat prostate after oral administration of this drug. The plasma concentration of silodosin after oral administration in rats and healthy volunteers was measured using a high-performance liquid chromatographic method. The alpha(1)-adrenoceptor-binding affinities (K(i)) of silodosin, tamsulosin, and terazosin in the human prostate and plasma concentrations of tamsulosin and terazosin were obtained from the literature. Using the alpha(1)-adrenoceptor binding parameters of silodosin in rat prostate, alpha(1)-adrenoceptor occupancy in the human prostate was estimated to be around 60-70% at 1-6 h after oral administration of silodosin at doses of 3.0, 8.1, and 16.1 micromol. Thereafter, the receptor occupancy was periodically decreased, to 24% (8.1 micromol) and 54% (16.1 micromol) 24 h later. A similar magnitude and time course of alpha(1)-adrenoceptor occupancy by silodosin in the human prostate were estimated using alpha(1)-adrenoceptor-binding affinities (K(i)) in the human prostate. Despite about two orders of differences in the plasma unbound concentrations after clinically effective oral dosages of silodosin, tamsulosin, and terazosin, there was a comparable magnitude of prostatic alpha(1)-adrenoceptor occupancy by these drugs. In conclusion, the prediction of alpha(1)-adrenoceptor occupancy in the human prostate by alpha(1)-adrenoceptor antagonists may provide the rationale for the optimum dosage regimen of these drugs in the therapy of BPH.

Authors+Show Affiliations

Department of Pharmacokinetics and Pharmacodynamics and Center of Excellence Program in the 21st Century, University of Shizuoka School of Pharmaceutical Sciences, Sizuoka, Japan. yamada@ys7-u-shizuoka-ken.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17603160

Citation

Yamada, Shizuo, et al. "Prediction of Alpha1-adrenoceptor Occupancy in the Human Prostate From Plasma Concentrations of Silodosin, Tamsulosin and Terazosin to Treat Urinary Obstruction in Benign Prostatic Hyperplasia." Biological & Pharmaceutical Bulletin, vol. 30, no. 7, 2007, pp. 1237-41.
Yamada S, Kato Y, Okura T, et al. Prediction of alpha1-adrenoceptor occupancy in the human prostate from plasma concentrations of silodosin, tamsulosin and terazosin to treat urinary obstruction in benign prostatic hyperplasia. Biol Pharm Bull. 2007;30(7):1237-41.
Yamada, S., Kato, Y., Okura, T., Kagawa, Y., & Kawabe, K. (2007). Prediction of alpha1-adrenoceptor occupancy in the human prostate from plasma concentrations of silodosin, tamsulosin and terazosin to treat urinary obstruction in benign prostatic hyperplasia. Biological & Pharmaceutical Bulletin, 30(7), 1237-41.
Yamada S, et al. Prediction of Alpha1-adrenoceptor Occupancy in the Human Prostate From Plasma Concentrations of Silodosin, Tamsulosin and Terazosin to Treat Urinary Obstruction in Benign Prostatic Hyperplasia. Biol Pharm Bull. 2007;30(7):1237-41. PubMed PMID: 17603160.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prediction of alpha1-adrenoceptor occupancy in the human prostate from plasma concentrations of silodosin, tamsulosin and terazosin to treat urinary obstruction in benign prostatic hyperplasia. AU - Yamada,Shizuo, AU - Kato,Yasuhiro, AU - Okura,Takashi, AU - Kagawa,Yoshiyuki, AU - Kawabe,Kazuki, PY - 2007/7/3/pubmed PY - 2007/8/19/medline PY - 2007/7/3/entrez SP - 1237 EP - 41 JF - Biological & pharmaceutical bulletin JO - Biol. Pharm. Bull. VL - 30 IS - 7 N2 - Alpha1-adrenoceptor antagonists are clinically useful for the improvement of urinary obstruction due to benign prostatic hyperplasia (BPH), and their therapeutic effects are mediated through the blockade of prostatic alpha(1)-adrenoceptors. The present study was undertaken to predict the magnitude and duration of alpha(1)-adrenoceptor occupancy in the human prostate after oral alpha(1)-adrenoceptor antagonists. Prostatic alpha(1)-adrenoceptor-binding parameters of silodosin were estimated by measuring specific [(3)H]prazosin binding in rat prostate after oral administration of this drug. The plasma concentration of silodosin after oral administration in rats and healthy volunteers was measured using a high-performance liquid chromatographic method. The alpha(1)-adrenoceptor-binding affinities (K(i)) of silodosin, tamsulosin, and terazosin in the human prostate and plasma concentrations of tamsulosin and terazosin were obtained from the literature. Using the alpha(1)-adrenoceptor binding parameters of silodosin in rat prostate, alpha(1)-adrenoceptor occupancy in the human prostate was estimated to be around 60-70% at 1-6 h after oral administration of silodosin at doses of 3.0, 8.1, and 16.1 micromol. Thereafter, the receptor occupancy was periodically decreased, to 24% (8.1 micromol) and 54% (16.1 micromol) 24 h later. A similar magnitude and time course of alpha(1)-adrenoceptor occupancy by silodosin in the human prostate were estimated using alpha(1)-adrenoceptor-binding affinities (K(i)) in the human prostate. Despite about two orders of differences in the plasma unbound concentrations after clinically effective oral dosages of silodosin, tamsulosin, and terazosin, there was a comparable magnitude of prostatic alpha(1)-adrenoceptor occupancy by these drugs. In conclusion, the prediction of alpha(1)-adrenoceptor occupancy in the human prostate by alpha(1)-adrenoceptor antagonists may provide the rationale for the optimum dosage regimen of these drugs in the therapy of BPH. SN - 0918-6158 UR - https://www.unboundmedicine.com/medline/citation/17603160/Prediction_of_alpha1_adrenoceptor_occupancy_in_the_human_prostate_from_plasma_concentrations_of_silodosin_tamsulosin_and_terazosin_to_treat_urinary_obstruction_in_benign_prostatic_hyperplasia_ L2 - http://joi.jlc.jst.go.jp/JST.JSTAGE/bpb/30.1237?from=PubMed DB - PRIME DP - Unbound Medicine ER -