Relationship between the functional effect of tamsulosin and its concentration in lower urinary tract tissues in dogs.
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 microg/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.
Sato
Shuichi
S
Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. shuichi.sato@jp.astellas.com
Ohtake
Akiyoshi
A
Hatanaka
Toshiki
T
Suzuki
Masanori
M
Matsushima
Hiroshi
H
Sasamata
Masao
M
Miyata
Keiji
K
D000284:Administration, Oral; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011467:Prostate / Q000378:metabolism; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000077409:Tamsulosin; D016896:Treatment Outcome; D014521:Urethra / Q000378:metabolism*; D001743:Urinary Bladder / Q000378:metabolism; D014563:Urodynamics / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D013449:Sulfonamides; D010656:Phenylephrine; D000077409:Tamsulosin