Therapeutic Research

平均全身血圧が40 mmHg以下に低下遷延すると発症する“ 出血性ショック心臓症候群（shock heart syndrome）”は，致死性の病態を呈する。“shock hear t syndrome”におけるリポソーム封入酸素運搬体（HbV）の慢性抗不整脈効果を検討した。方法：SDラット（n＝47）で，femoral ar teryから脱血・蘇生液投与を施行し30％再出血性ショックモデルを作成した。蘇生液は5％アルブミン（ALB群），洗浄赤血球（wRBC群）およびHbV（HbV群）とした。26 ラットで約1 ～2 週間後の生存率を検討し，生存ラットの心筋（各群n＝ 7）を摘出してランゲンドルフ灌流心として心筋活動電位を可視化できるdi –4–ANEPPSで染色し，光工学的手法（OMP）にて，活動電位の伝搬様式・伝搬速度，および再分極過程の均一性を示す指標（action potential duration dispersion［APDd］）を測定した。電気生理検査であるburst pacing にて致死性心室性不整脈（VT/VF）誘発の有無とOMP指標との関係も検討した。　結果：ALB群の生存率は，wRBC群・HbV 群に比較し有意に低かった。OMP解析では，ALB群でwRBC群・HbV群に比べ伝導様式の異常と伝導速度の遅延が認められる傾向があり，ALB群で全例VT/VF が誘発された。wRBC 群・HbV群では誘発されなかった。APDdは，ALB群で他の2 群に比し延長していた（23.3±9.7 msvs 12.9±2.7 ms, 15.3±4.2 ms, p＜0.01）。結語：“shock heart syndrome”ラットモデルにて，HbV は慢性期においても，APDdの延長抑制効果を介して，wRBCと同等の予後改善効果と抗不整脈効果が認められることが示唆された。

Objective：We conducted a post‒marketing surveillance to investigate the safety and efficacy of atovaquone under actual conditions of use for the treatment of patients with Pneumocystis pneumonia（PCP）or prevention of PCP. Method：All patients who received atovaquone after the start of its distribution were included in the surveillance. The duration of the observation was 21 days at a maximum for PCP treatment and one year at a maximum for PCP prevention. Safety was evaluated based on the occurrence of adverse drug reactions（ADRs）, and efficacy was assessed based on the investigator’s global assessment for PCP treatment, and the development of PCP for PCP prevention.Results：The incidence of ADRs was 23.20％（29/125）for PCP treatment and 13.99％（20/143）for PCP prevention in patients with human immunodeficiency virus （HIV）, and 19.25％（51/265）for PCP treatment and 18.50％（96/519）for PCP prevention in non‒HIV patients. Common ADRs were rash, drug eruption, hepatic function abnormal and diarrhea. The responder rates were 88.14％（104/118）for PCP treatment and 100.00％（134/134）for PCP prevention in the HIV patients, and 83.54％（203/243） for PCP treatment and 99.80％（492/493）for PCP prevention in the non‒HIV patients. Conclusion：The results of this surveillance revealed no new safety or efficacy concern for both PCP treatment and prevention, and suggested that atovaquone would be a useful alternative drug when the use of sulfamethoxazole‒trimethoprim combination would be difficult.

Objectives：To understand the safety and the efficacy of Atovaquone in immunocompromised diseases, we conducted additional subgroup analyses of Atovaquone post market study. Methods：Atovaquone post market study was conducted from April 2012, to March 2016, and 1,061 patient reports were collected. Amongst 787 cases were non‒HIV patients, 265 patients were diagnosed as PCP and Atovaquone was used for their treatment. Remaining 519 cases were potential immunocompromised patients and Atovaquone was prescribed for PCP prevention purpose. Results：Top five background diseases were selected, and efficacy and safety of each category was independently analyzed. Further in each category, analysis was performed separately for the treatment and the prevention purpose. These five categories were “malignancy‒related disease（PCP treatment：n ＝74, PCP prevention：n＝222）,” “autoimmune and collagen disease‒related disease（110, 183）,”“respiratory disorder （53, 104）,”“rheumatoid arthritis（61, 28）”and“interstitial lung disease（41, 74）”. As a result of sub‒analysis, there were subgroups with a high incidence of hepatobiliary disorders and those with a low incidence. It was suggested that the onset of hepatobiliary disorders is more likely to be associated with the presence of complication by hepatic dysfunction or advanced age rather than with the influence of the background diseases. Conclusions：Our subgroup analyses clarified that Atovaquone is useful alternative for trimethoprim‒sulfamethoxazole for non‒HIV patients. However, careful monitoring of complications is necessary for patients with hepatic dysfunction or elderly population.