Doripenem の眼組織移行性と眼科領域感染症に対する臨床効果  [in Japanese] Study of doripenem distribution in ocular tissue and its clinical relevance in ophthalmological infection  [in Japanese]

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Abstract

新規注射用カルバペネム系抗菌薬doripenem (DRPM) 250mg点滴静脈内投与時の本薬の眼組織 (前房水) への移行性を検討した。また, 眼科領域感染症として角膜潰瘍, 眼窩感染および眼内炎の患者へDRPM250mgを1日2回または3回, あるいは500mgを1日2回点滴静脈内投与した時の本薬の有効性および安全性の検討を行った。<BR>1. 組織移行性試験<BR>白内障手術施行患者へのDRPM点滴静脈内投与開始70~115分後の前房水中DRPM濃度は0.16~0.87μg/mL, またほぼ同時期の血漿中の本薬の濃度は6.86~12.9μg/mLであった。<BR>2. 第III相一般臨床試験<BR>1) 有効性<BR>評価対象は15例 (角模潰瘍10例, 眼窩感染4例, 眼内炎1例)。1日投与量別の症例数は250mg×2回投与が9例, 250mg×3回投与および500mg×2回投与が, おのおの3例で, 臨床効果における有効率は100.0%(15/15例) であった。<BR>投与前後で菌の消長が検討可能であった症例は8例 (角膜潰瘍4例, 眼窩感染3例, 眼内炎1例) であった。これら8例の内訳はα-<I>Streptococcus</I>感染例が1例, C<I>orynebacterium</I> sp.感染例が3例, <I>Pseudomonas aerugimosa</I>感染例が2例, <I>Propionibacterium acnes</I>感染例が1例および<I>Staphylococcus aurens</I>と<I>Prevotella intermedia</I>の混合感染例が1例であり, これら8例全例において原因菌はすべて消失した。また, 投与後出現菌は認められなかった。<BR>2) 安全性<BR>評価対象は本薬を投与した全症例の15例で, 主要評価項目として副作用 (症状, 臨床検査値) の有無を検討した。<BR>有害症状が4例 (8件) に認められたが, 軽度または中等度で, 副作用 (症状) と判定された症例はなかった。<BR>臨床検査値異常変動が5例 (5件) に認められ, これらすべては治験薬との因果関係が否定されなかった。このため, 副作用 (臨床検査値) は, 5例 (5件: アラニンアミノトランスフェラーゼ上昇3件, アスパラギン酸アミノトランスフェラーゼ上昇, γ-グルタミルトランスペブチダーゼ上昇, 各1件) となり, 発現率は33.3%(5/15例) であった。程度はすべて軽度で, 転帰はすべて正常化であった。なお, これらの副作用 (臨床検査値) の多くは類薬での療法において認められている事象と同様の事象であった。

We studied the distribution of doripenem (DRPM), a new carbapenem antibiotic for injection, in ocular tissue (aqueous humor) after DRPM infusion at a dosage of 250mg, and evaluated the efficacy and safety of DRPM administered in patients with corneal ulcer, orbital infection, and endophthalmitis after DRPM infusion at a dosage of 250mg, b. i. d. or t. i. d., or at 500mg, b. i. d.<BR>DRPM concentration in the aqueous humor of those undergoing cataract surgery was 0.16-0.87mg/mL within 70-115 minutes of the start of infusion. Plasma concentration in the same period was 6.86-12.9μg/mL.<BR>Of 15 patients evaluated for efficacy-corneal ulcer in 10, orbital infection in 4, and endophthalmitis in 1-DRPM was administered to 9 at a dose of 250mg b. i. d., to 3 at a dose of 250mg t. i. d., and to 3 at a dose of 500mg b. i. d. Clinical efficacy, the primary endpoint in this study, was 100.0%(15/15). Improvement on Day 2, a secondary endpoint, was 100%(15/15).<BR>Bacteriological response was evaluated in 8 patients-corneal ulcer in 4, orbital infection in 3 and endophthalmitis in 1-1 of whom had α-<I>Streptococcus</I> infection, 3 <I>Corynebacterium</I> sp. infection, 2 <I>P. aeruginosa</I> infection, 1 <I>P. acnes</I> infection, and 1 <I>S. aureus-P</I>. <I>intermedia</I> mixed infection. Causative bacteria were eradicated in all 8 and no new strains appeared after DRPM administration.<BR>All 15 were evaluated for safety, with the primary endpoint the absence or presence of adverse drug reactions (symptoms and laboratory findings) and the secondary endpoint overall safety. In 4, the 8 adverse events observed were mild to moderate and none was judged to be related to DRPM. In the abnormal laboratory findings reported in 5 (5 events), the causal relationship to DRPM could not be ruled out resulting in these 5 adverse events judged to be adverse drug reactions (abnormal laboratory findings), including an increase in ALT (3 events), an increase in AST (1), and an increase in γ-GPT (1). The incidence of adverse drug reactions was 33.3%(5/15) and all were mild and returned to normal. Many of these adverse drug reactions (abnormal laboratory findings) were similar to those of currently available carbapenem antibiotics. The overall safety of DRPM was 100.0%(15/15).

Journal

  • Japanese Journal of Chemotherapy

    Japanese Journal of Chemotherapy 53, 313-322, 2005-07-20

    Japanese Society of Chemotherapy

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