Relationship between the Functional Effect of Tamsulosin and Its Concentration in Lower Urinary Tract Tissues in Dogs(Pharmacology)
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概要
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We investigated the relationship between the pharmacological effect of tamsulosin and its concentrations in plasma and several lower urinary tract (LUT) and arterial tissues in conscious male dogs. Oral administration of tamsulosin (30 and 100μg/kg) inhibited phenylephrine-induced intraurethral pressure (IUP) elevation. Inhibition peaked at 1, 2 h after dosing and lasted up to 6-8 h. Basal mean blood pressure did not significantly change throughout the observation period. Plasma concentration reached maximum within 0.5 h after dosing, whereas that in LUT tissues (prostate, urethra and bladder) reached maximum at l, 2 h, and prostatic and urethral concentrations remained higher than those in plasma and arterial tissues at almost all observation points. Prostatic concentrations of tamsulosin at individual time points were 2.2- to 18.0-fold higher than plasma and 3.7- to 12.3-fold higher than mesenteric artery concentrations. Urethral concentrations of tamsulosin were also higher than those in both plasma and mesenteric artery; The prostatic and urethral concentrations of tamsulosin correlated well with its effect on IUP response [r^2=0.98 (p<0.01) and r^2=0.99 (p<0.01), respectively]. Our data demonstrate that tamsulosin is selectively retained in LUT tissues compared with plasma and arterial tissues and that its sustained effect on IUP response appears to be related to the prostatic and urethral retention of tamsulosin.
- 公益社団法人日本薬学会の論文
- 2007-03-01
著者
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SASAMATA Masao
Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
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MIYATA Keiji
Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
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Miyata Keiji
Applied Pharmacology Res. Laboratories Drug Discovery Res. Astellas Pharma Inc. Jpn
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Miyata Keiji
Pharmacology Laboratories Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.
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Sasamata Masao
Applied Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.
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Sasamata Masao
Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.
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Suzuki Masanori
Pharmacology Research Labs. Drug Discovery Research Astellas Pharma Inc.
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OHTAKE Akiyoshi
Pharmacology Research Labs., Drug Discovery Research, Astellas Pharma Inc.
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SATO Shuichi
Pharmacology Research Labs., Drug Discovery Research, Astellas Pharma Inc.
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HATANAKA Toshiki
Development, Astellas Pharma Inc.
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SUZUKI Masanoni
Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
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MATSUSHIMA Hiroshi
Development, Astellas Pharma Inc.
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HATANAKA Toshiki
Pharmacology Research Labs., Drug Discovery Research, Astellas Pharma Inc.
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Hatanaka Toshiki
Pharmacology Research Labs. Drug Discovery Research Astellas Pharma Inc.
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Matsushima Hiroshi
Development Astellas Pharma Inc.
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Sato Shuichi
Applied Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.
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Ohtake Akiyoshi
Applied Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.
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