DOSE-RESPONSE EFFECT OF INTRATHECAL ALFENTANIL ON CANINE LOWER URINARY-TRACT DYNAMICS

The effect of intrathecal (IT) administration of three different doses (1, 2.5, and 5 mug/kg) of alfentanil on lower urinary tract dynamics was examined by urodynamic studies, cystometrograms (CMG), and urethra l pressure profiles (UPP) in seven anesthetized dogs. Simultaneous ser um drug concentrations were determined by specific radioimmunoassay fo r time-response analysis. A significant dose-dependent relaxation of u rethral musculature expressed by a reduction in UPP values of 41.5% an d 38.4% (P < 0.03) was noted 30 min after 5 and 2.5 mug/kg IT alfentan il, respectively, whereas the decrease of 13.4-22% in mean CMG values was not significant. All changes in UPP and CMG returned to baseline v alues by 60 min. The pharmacokinetics of alfentanil from the cerebrosp inal fluid to the systemic circulation were linear, i.e., dose-indepen dent with maximal serum concentrations of 0.6, 1.4, and 3.5 ng/mL 10 m in after the three respective IT doses. The low serum alfentanil conce ntrations and the lack of time correlation between the peak values and the changes in urinary tract activity, point to a spinally mediated m echanism. The short-lived effect of IT alfentanil on lower urinary tra ct dynamics and the relaxation of the bladder neck allow for unobstruc ted micturition pathways and may avoid urinary retention.