ADULT UROLOGY EFFECT OF DOSING REGIMEN ON EFFICACY AND SAFETY OF DOXAZOSIN IN NORMOTENSIVE MEN WITH SYMPTOMATIC PROSTATISM: A PILOT STUDY STEVEN A. KAPLAN, M.D. KATHERINE A. SOLDO, R.N. CARL A. OLSSON, M.D. From the Department of Urology, College of Physicians & Surgeons, Columbia University, New York, New York ABSTRACT--Objectives. In this pilot study, the effect of dosing schedule on the efficacy and safety of the long-acting alpha 1-adrenergic blocker doxazosin (DOX) was evaluated in 48 consecutive, normotensive men (mean age, 61.2 years) with symptoms of prostatism. Methods. In this titration to fixed dose study, patients were randomized into 1 of 4 treatment groups: (1) 4 mg DOX once in the AM (n --- ] 2); (2) 4 mg DOX once in the PM (n = 12); (3) 8 mg DOX once in the AM (n = 12); and (4) 8 mg DOX once in the PM (n = 12). Parameters evaluated included Boyarsky symptom score (Sx), peak uroflow (Qmax)' blood pressure, and occurrence of side effects. Once stabilized, patients were seen at 3-month intervals; follow-up ranged from 3 to 19 months (mean, 7.7). Results. Clinical improvement as determined by Sx and Qmax was similar for AM and PM groups with either 4 or 8 mg of DOX. Mean decreases in Sx at 3 months were 4.6, 4.2, 5.1, and 5.2 and at 6 months were 4.7, 4.7, 5.3, and 5.4 for the 4 mg AM, 4 mg PM, 8 mg AM, and 8 mg PM, respectively. Mean peak uroflow at 3 months increased 2.7, 2.9, 3.2, and 3.3 mL/s and at 6 months increased 2.6, 3.0, 3.4, and 3.5 mUs for the 4 mg AM, 4 mg PM, 8 mg AM, and 8 mg PM, respectively (p < 0.05). Six patients (13%) were dropped from the study because of side effects (2 for fatigue, 2 for headache, 2 for dizzi- ness): 5 during the titration phase (4 mg AM: 2; 8 mg AM: 2; 8 mg PM: 1), and 1 during the treatment phase (8 mg AM). Conclusions. These data suggest that evening dosing does not diminish efficacy yet may enhance toleration of DOX. These preliminary results suggest that a larger prospec- tive study is warranted to determine the optimal dosing and timing of DOX in the man- agement of symptomatic benign prostatic hyperplasia. The contractile properties of prostatic smooth muscle are mediated primarily by alpha~- adrenoreceptors found in large quantities in the prostatic stroma and capsule. 1 Sympathetic stimu- lation of these receptors increases smooth muscle tone, previously termed the dynamic component of prostatism. Relaxation or blockade of these re- ceptors decreases this dynamic component and contributes to both subjective and objective im- provement. 2 Submitted: November 22, 1993, accepted (with revisions): April 22, 1994 Alpha-blockade in the management of symp[~ matic prostatism has had variable success; it all~ viates acute symptoms associated with prostat[~ smooth muscle tone.l-4 There have been multipl~ reports of significant improvement in both syrn~ toms and urodynamic parameters; however, cli~) cal improvement is offset in some patients b:~ significant adverse events, including postural h~ potension, dizziness, and asthenia. 1-7 Recentl~ newer long-acting alphal-adrenergic blockers su~ as terazosin (h/2 = 12 hours) and doxazosin (tw 22 hours) have been reported to improve symf toms and uroflow in men with prostatism. 2'4-6 It! 348 UROLOG'¢ / SE.P:rEMB~e 1994/ VOLUME 44, NUMB~.I~