RT Journal Article
SR Electronic
T1 Pharmacological Effect of Tamsulosin in Relation to Dog Plasma and Tissue Concentrations: Prostatic and Urethral Retention Possibly Contributes to Uroselectivity of Tamsulosin
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 697
OP 703
VO 296
IS 3
A1 Shuichi Sato
A1 Akiyoshi Ohtake
A1 Hiroshi Matsushima
A1 Chikashi Saitoh
A1 Shinji Usuda
A1 Keiji Miyata
YR 2001
UL http://jpet.aspetjournals.org/content/296/3/697.abstract
AB In the present study the pharmacokinetics and pharmacodynamics of tamsulosin were investigated in anesthetized male dogs. Hypogastric nerve stimulation elevated the intraurethral pressure (IUP), which was inhibited dose dependently by intraduodenal administration of tamsulosin (3–30 μg/kg). The inhibition peaked about 90 min after dosing and lasted up to 240 min. The basal mean blood pressure did not change significantly during the observation period. The plasma, prostatic, and urethral concentrations of tamsulosin were determined by the liquid chromatography-mass spectrometry/mass spectrometry method. The plasma concentration reached the maximal level within 30 min after dosing and gradually declined thereafter. The maximal total plasma concentration of tamsulosin (Cmax, t) and its unbound concentration (Cmax, u) correlated with the maximal effect on IUP response [r2 = 0.81 (p < 0.01, n = 15) andr2 = 0.84 (p < 0.01, n = 15), respectively]. Each individual unbound plasma concentration did not correlate, however, with its associated inhibition of IUP response (r2 = 0.04, n = 126). Although the plasma concentration of tamsulosin decreased nearly to the lower limit of quantitation 240 min after dosing, the prostatic and urethral concentrations remained high, i.e., 13 to 44 times greater than the plasma concentration. Our data demonstrate that the maximal inhibition by tamsulosin of IUP response is well correlated with the maximal plasma concentration in the early phase. The sustained effect of tamsulosin on IUP response that follows may be related to prostatic and urethral retention of tamsulosin. The American Society for Pharmacology and Experimental Therapeutics