Relationship between the Functional Effect of Tamsulosin and Its Concentration in Lower Urinary Tract Tissues in Dogs

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  • Sato Shuichi
    Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
  • Ohtake Akiyoshi
    Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
  • Hatanaka Toshiki
    Development, Astellas Pharma Inc.
  • Suzuki Masanori
    Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
  • Matsushima Hiroshi
    Development, Astellas Pharma Inc.
  • Sasamata Masao
    Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
  • Miyata Keiji
    Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.

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説明

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 100 μg/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 1, 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 [r2=0.98 (p<0.01) and r2=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.

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