前立腺肥大症に伴う排尿障害に対する塩酸テラゾシンの臨床的検討 : 漸増法による多施設共同オープン試験

Abstract

1)テラゾシンの前立腺肥大症に伴う排尿障害に対する臨床効果および副作用について, 91例, 18施設の多施設臨床試験を実施した.試験は1週間以上の観察期, 6週間の治療期とし, 観察期および治療2週目, 4週目, 6週目に自覚症状, 他覚所見(尿流量率, 排尿量, 残尿量)の変化を評価した.超音波断層法, 尿道造影, CTスキャンなどで前立腺の推定重量を求め, 前立腺の大きさと本剤の効果についても検討した.観察期にはプラセボ錠を投与し, 治療は塩酸テラゾシン1 mg/日を初期投与量とし2週目で自覚症状が改善以上であれば1 mg/日の投与量を維持し, やや改善以下であれば2 mg/日に増量, 4週目で改善以上であれば2 mg/日の投与量を維持し, やや改善以下であれば4 mg/日に増量し, 6週目に最終効果判定をする.1 mg→2 mg→4 mgの漸増法とした.2)自覚症状の累積改善率は, 1 mg/日では18.5%, 2 mg/日までで55.6%, 4 mg/日までで65.4%であった.観察期の自覚症状の強いものの方が症状の改善度が高く, 治療終了時には自覚症状スコアは観察期のスコアにかかわらずほぼ同じレベルに収束した.3)自排尿量, 最大尿流量率, 平均尿流量率, 残尿率, ノモグラムスコアは, いずれも治療後有意に改善した.残尿量, 排尿開始までの時間については有意差はえられなかった.前立腺重量と最大尿流量率, ノモグラムスコアの改善度の間に有意な相関は認めなかった.他覚所見の累積改善率は, 1 mg/日では13.2%, 2 mg/日までで42.1%, 4 mg/日までで50.0%であった.4)全般改善度の累積改善率は, 1 mg/日14.5%, 2 mg/日までで50.0%, 4 mg/日までで61.8%であった.5)副作用は, ふらつき6件, 立ちくらみ2件, 耳鳴り, むかつき, かすみ目各1件の計11件(10例)で, 発現率は11.6%であった.5例は臨床上問題なく服薬を継続し, 1例は減量して服薬を継続した.服薬を中止したのは4例, 4.7%であった.本薬に起因すると思われる臨床検査値異常は認められなかった.拡張期血圧の有意な低下を認めたが, 収縮期血圧, 脈拍に有意な変動を認めなかった

In this study the multicenter, fixed-flexible dose regimen was taken to evaluate the effective dose range of Terazosin for the treatment of micturition disturbance in benign prostatic hypertrophy (BPH) and to clarify the characteristics of patients who are more responsive to Terazosin therapy. After a 1-week washout (placebo) the first two weeks 1 mg/day of Terazosin was administered, then depending on efficacy of subjective symptoms, Terazosin doses were increased up to 2 mg/day and 4 mg/day at intervals of two weeks. After six weeks the final efficacy and safety were assessed. The subjective symptom improvement rate was 18.5% by 1 mg/day, 55.6% by 2 mg/day and 65.4% by 4 mg/day cumulatively. The objective symptom improvement rate were 13.2% by 1 mg/day, 42.1% by 2 mg/day and 50.0% by 4 mg/day cumulatively. The global improvement rate was 14.5% by 1 mg/day, 50.0% by 2 mg/day and 61.8% by 4 mg/day cumulatively. The patients who had a higher subjective symptom score in the lead-in period were more improved rather than those who had a lower score. In objective symptoms, voided volume, maximum flow rate (MFR), MFR nomogram score and average flow rate improved and the ratio of residual urine volume decreased. There was no relationship between clinical improvement on either subjective or objective symptoms and prostatic weight. Adverse reactions, such as dizziness, vertigo, tinnitus, nausea and blurred vision; were seen in 10 cases. In conclusion Terazosin was effective and well tolerated for the treatment of patients who had micturition disturbance with BPH in the dose range of 2 to 4 mg/day.