Pharmacological effect of tamsulosin in relation to dog plasma and tissue concentrations: Prostatic and urethral retention possibly contributes to uroselectivity of tamsulosin

In the present study the pharmacokinetics and pharmacodynamics of tamsulosi n were investigated in anesthetized male dogs. Hypogastric nerve stimulatio n elevated the intraurethral pressure (IUP), which was inhibited dose depen dently by intraduodenal administration of tamsulosin (3-30 mug/kg). The inh ibition peaked about 90 min after dosing and lasted up to 240 min. The basa l mean blood pressure did not change significantly during the observation p eriod. The plasma, prostatic, and urethral concentrations of tamsulosin wer e determined by the liquid chromatography-mass spectrometry/mass spectromet ry method. The plasma concentration reached the maximal level within 30 min after dosing and gradually declined thereafter. The maximal total plasma c oncentration of tamsulosin (C-max,C-t) and its unbound concentration (C-max ,C-u) correlated with the maximal effect on IUP response [r(2) = 0.81 (p< 0 .01, n = 15) and r(2) = 0.84 (p< 0.01, n = 15), respectively]. Each individ ual unbound plasma concentration did not correlate, however, with its assoc iated inhibition of IUP response (r(2) = 0.04, n = 126). Although the plasm a concentration of tamsulosin decreased nearly to the lower limit of quanti tation 240 min after dosing, the prostatic and urethral concentrations rema ined 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 re lated to prostatic and urethral retention of tamsulosin.