OBJECTIVES: This single-centre, double-blind, randomized parallel-group study compared ambulatory blood pressure (AMBP) and heart rate (HR) profiles and responses to orthostatic testing (OT) for recommended regimens of tamsulosin (TAM, modified release formulation) and terazosin (TER), two alpha1-adrenoceptor antagonists that differ in their selectivity for alpha1-adrenoceptor subtypes, pharmacokinetic properties and recommended posology for the treatment of lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO). METHODS:50 elderly normotensive male volunteers (mean age 68 years, range 61-78; 27 had LUTS) entered a single-blind 24-hour placebo run-in followed by a 15-day double-blind treatment in which the TER group received a 1-week treatment with 1 mg, then 1 week with 2 mg and finally a last dose of 5 mg, each dose administered once daily in the evening, while TAM subjects received 0.4 mg once daily after breakfast throughout. Subjects had AMBPs and OT while hospitalized on four occasions: during the placebo run-in and subsequent to the first dose of 1, 2 and 5 mg TER or at corresponding times under TAM. Regular OT (blood pressure after 5 min supine and after 2 min standing) was carried out between 6:00 and 6:30 a.m.; 'nocturial' OT took place whenever the subject had to leave the bed at night to void. RESULTS: The baseline blood pressure values were slightly higher in the TAM group, but under treatment there was little difference between the treatments with regard to circadian changes in AMBP and HR. Under TER, there were 10 incidents of symptomatic hypotensive OT in 9 subjects (2 with syncope); furthermore, there were 24 events of asymptomatic exaggerated (> or = 20 mm Hg) decrease in systolic blood pressure in 12 subjects. With TAM in contrast, there was only 1 subject who experienced symptomatic hypotensive OT on 3 occasions (this subject had a previous history of vertigo and ought not to have been included); 7 subjects on TAM showed 16 incidents of asymptomatic hypotensive OT. The difference between TER and TAM was statistically significant for the number of subjects with positive symptomatic OT (p = 0.011). CONCLUSION: Once-daily dosing of TAM after breakfast at a fixed dose level (0.4 mg) offers a more efficient protection against undesired cardiovascular extension effects in the normotensive elderly treated for LUTS suggestive of BPO than the usually recommended treatment schedule of TER with step-up doses (1-5 mg) administered at night.
RCT Entities:
OBJECTIVES: This single-centre, double-blind, randomized parallel-group study compared ambulatory blood pressure (AMBP) and heart rate (HR) profiles and responses to orthostatic testing (OT) for recommended regimens of tamsulosin (TAM, modified release formulation) and terazosin (TER), two alpha1-adrenoceptor antagonists that differ in their selectivity for alpha1-adrenoceptor subtypes, pharmacokinetic properties and recommended posology for the treatment of lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO). METHODS: 50 elderly normotensive male volunteers (mean age 68 years, range 61-78; 27 had LUTS) entered a single-blind 24-hour placebo run-in followed by a 15-day double-blind treatment in which the TER group received a 1-week treatment with 1 mg, then 1 week with 2 mg and finally a last dose of 5 mg, each dose administered once daily in the evening, while TAM subjects received 0.4 mg once daily after breakfast throughout. Subjects had AMBPs and OT while hospitalized on four occasions: during the placebo run-in and subsequent to the first dose of 1, 2 and 5 mg TER or at corresponding times under TAM. Regular OT (blood pressure after 5 min supine and after 2 min standing) was carried out between 6:00 and 6:30 a.m.; 'nocturial' OT took place whenever the subject had to leave the bed at night to void. RESULTS: The baseline blood pressure values were slightly higher in the TAM group, but under treatment there was little difference between the treatments with regard to circadian changes in AMBP and HR. Under TER, there were 10 incidents of symptomatic hypotensive OT in 9 subjects (2 with syncope); furthermore, there were 24 events of asymptomatic exaggerated (> or = 20 mm Hg) decrease in systolic blood pressure in 12 subjects. With TAM in contrast, there was only 1 subject who experienced symptomatic hypotensive OT on 3 occasions (this subject had a previous history of vertigo and ought not to have been included); 7 subjects on TAM showed 16 incidents of asymptomatic hypotensive OT. The difference between TER and TAM was statistically significant for the number of subjects with positive symptomatic OT (p = 0.011). CONCLUSION: Once-daily dosing of TAM after breakfast at a fixed dose level (0.4 mg) offers a more efficient protection against undesired cardiovascular extension effects in the normotensive elderly treated for LUTS suggestive of BPO than the usually recommended treatment schedule of TER with step-up doses (1-5 mg) administered at night.
Authors: Joachim Troost; Shinji Tatami; Yasuhiro Tsuda; Michaela Mattheus; Ludwig Mehlburger; Martina Wein; Martin C Michel Journal: Br J Clin Pharmacol Date: 2011-08 Impact factor: 4.335