肺高血圧症例におけるトロンボキサン合成酵素阻害剤（OKY−046：オザグレル）の血中プロスタノイドに及ぼす影響および臨床効果

Effect of Thromboxane Synthetase Inhibitor, OKY-046, on the Plasma Prostanoid and Clinical Symptoms in Pulmonary Hypertension

　肺高血圧症例に対してトロンボキサン合成酵素阻害剤（オザグレル）を経口投与し，投与前後の血中プロスタノイドの推移と臨床効果を検討した．対象は原発性肺高血圧症3例，二次性肺高血圧症6例で，投与開始年齢8〜41（20.1±9.8）歳，投与期間2.7±1.5年，投与量200〜400mg／dayであった．トロンボキサンA₂（TXA₂）とプロスタサイクリン（PGI₂）各々の代謝産物であるTXB₂および6—keto-PGF_1αの血漿中濃度をオザグレル投与前後でRIA法にて測定した．投与前の血漿中TXB₂は平均75.1±69.6pg／ml,6—keto-PGF_1αは35.8±56.2pg／mlで，TXB₂／6—keto-PGF_1α比は5.3±3.9と高値を示した．この比は7例で投与開始後2〜6ヵ月の時点で既に低下を認め，TXA₂とPGI₂の不均衡が改善されたものと考えられた．臨床症状の改善は6例に認められ，有効と考えられた．

Thromboxane synthetase inhibitors have been shownto reduce thromboxane (TXA₂), a potent vasocon-strictor and stimulus for platelet aggregation, andincrease prostacyclin (PGI₂) that acts as a physiologicalantagonist of TXA₂. In patients with pulmonary hyper-tension, an imbalance of TXA₂ and PGI₂ may exist.Furthermore, it may play a part in the development andmaintenance of the pathophysiology of pulmonaryhypertension.

We evaluated the effects of the TXA₂ synthetaseinhibitor (OKY-046) orally administered at 200~400mg/day in 3 patients with primary pulmonary hyper-tension (PPH) and 6 patients with secondary pulmonaryhypertension (SPH).

Plasma thromboxane B₂ (TXB₂) levels (the stablemetabolic product of TXA₂) were reduced, and plasma6-keto-PGF_1α, levels (the stable metabolic product of PGI₂) were increased after administration of OKY-046.The increased plasma TXB₂/6-keto-PGF_1α ratio wassignificantly reduced and returned to normal afteradministration of the OKY-046. In 6 cases, clinicalsymptoms were improved. A tendency towards bleedingwas observed as a side effect in 2 cases, but it resolveditself rapidly after the dose was reduced.

These results suggested that TXA₂ synthetase in-hibitor improves the imbalance of TXA₂ and PGI₂, andmay improve clinical symptoms in patients with pulmo-nary hypertension.