呼吸器感染症に対するNM441の基礎的,臨床的検討  [in Japanese] Basic and clinical studies on NM441 in respiratory tract infection  [in Japanese]

Access this Article

Search this Article

Author(s)

Abstract

新しく開発されたプロドラッグ型のキノロン系合成抗菌薬であるNM441の有用性を基礎的, 臨床的に検討した。<BR>1) 抗菌力: 当科保存の呼吸器感染症分離株に対するNM441の抗菌活性本体であるNM394, ofloxacin (OFLX), ciprofloxacin (CPFX), tosufloxacin (TFLX), sparfloxacin (SPFX) 5薬剤のMICを測定した。<BR><I>Streptococcis pneumoniae</I> (20株) に対するNM394の抗菌力はCPFXと同等で, OFLX, TFLX, SPFXよりやや劣っていた。<I>Klebsiella pneumoniae</I> (20株) に対してはCPFX, TFLXと同等で, OFLX, SPFXより優れていた。<I>Haemophilus</I> spp.(21株) に対してはCPFXよりやや劣るものの, OFLX, TFLX, SPFXと同等であった。<I>Pseudomonas aeruginosa</I> (20株) に対してはCPFX, TFLXよりやや劣るものの, SPFXと同等で, OFLXより優れていた。しかしながら, <I>Staphylococcns aureus</I> (20株) に対する抗菌力は他剤同様不十分であった。<BR>2) 体液中濃度測定: 喀痰への移行は慢性気管支炎1例に対して行い, 1回300mgを1日2回, 5日間投与し, 開始日, 3日目, 5日目の血清中, 喀痰中NM394の濃度を測定した。血清中濃度のピークは開始日, 3日目, 5日目とも投与4時間後にみられ, その値は1.43, 3.45, 2.86μg/mlであった。喀痰中濃度のピークは開始日, 3日目は投与6時間後, 5日目は投与1時間前 (起床後1回目の喀出痰) にみられ, その値は2.64, 7.49, 6.40μg/mlであった。血清より喀痰への移行率は185~224%と良好な値を示した。<BR>3) 臨床的検討: 呼吸器感染症12例 (急性肺炎1例, マイコプラズマ肺炎1例, 慢性気管支炎4例, 気管支拡張症3例, 気管支喘息の二次感染3例) に対して, 1回100~300mg, 1日2回, 5~14日間経口投与した。臨床効果は「著効」1例 (急性肺炎1例), 「有効」7例 (マイコプラズマ肺炎1例, 慢性気管支炎3例, 気管支喘息の二次感染3例), 「やや有効」1例 (慢性気管支炎1例), 「無効」3例 (気管支拡張症3例) で, 有効率は66.7%であった。副作用は認められず, 臨床検査値の異常変動はGOT・GPTの上昇1例, ALP・γ-GTP・LAPの上昇1例の計2例に認められた。

Basic and clinical studies on NM441, a new prodrug type quinolone, were performed and the following results were obtained.<BR>1. <I>In vitro</I> antimicrobial activity<BR>The minimum inhibitory concentrations (MICs) of NM394, the active form of NM441 were measured for 101 strains of 5 clinically isolated species and compared to those of ofloxacin (OFLX), ciprofloxacin (CPFX), tosufloxacin (TFLX) and sparfloxacin (SPFX). The activity of NM394 against <I>Streptococcus pneumoniae</I> was equal to that of CPFX but less than that of OFLX, TFLX and SPFX. NM394 showed better activity against <I>Klebsiella pneumoniae</I> than OFLX and SPFX and the activity was equal to that of CPFX and TFLX. The activity of NM394 against <I>Haemophilus</I> spp. was equal to that of OFLX, TFLX and SPFX but less than that of CPFX. NM394 showed better anti-pseudomonal activity against <I>Pseudomonas aeruginosa</I> than OFLX and the activity was equal to that of SPFX but less than that of CPFX and TFLX. None of them showed meaningful activity against <I>Staphylococcus aureus</I>.<BR>2. The penetration into sputum and serum<BR>NM441 was orally administered to a chronic bronchitis patient at a dose of 300mg twice a day for 5 days. The serum and sputum levels of NM394 were determined on the first, 3rd and 5th day of the administrations. The maximum serum levels were obtained 4 h after each administration on the first, 3rd and 5th days and the values were 1.43, 3.45 and 2.86μg/ml, respectively. The maximum sputum levels were obtained 6 h after the first and 3rd day of the administrations, but on the 5th day the peak was obtained in the first sputum in the morning, which was 1 h prior to the administration. Those values were 2.64, 7.49 and 6.40μg/ml, respectively. The penetration rate to the sputum was 185-224% higher than that to the serum.<BR>3. Clinical efficacy<BR>NM441 was administered to a total of 12 patients with respiratory tract infections at 100-300mg twice a day for 5-14 days. The clinical efficacy was evaluated as excellent in 1 acute pneumonia, good in 7 cases (1 mycoplasma pneumonia, 3 chronic bronchitis and 3 secondary infections to bronchial asthma), fair in 1 chronic bronchitis and poor in 3 cases (3 bronchiectasis). The clinical efficacy rate was 66.7%. No side effects were observed but abnormal laboratory findings were observed in 1 case in GOT·GPT elevation and in 1 case in ALP·γ-GTP·LAP elevation.

Journal

  • Japanese Journal of Chemotherapy

    Japanese Journal of Chemotherapy 44, 243-248, 1996-03-01

    Japanese Society of Chemotherapy

References:  6

Codes

Page Top