健康成人志願者とじん機能障害患者におけるネチルマイシン筋注時の薬動力学的研究

• Published in: CHEMOTHERAPY Vol. 30; no. 8; pp. 880 - 887
• Main Authors: YAMASAKU FUSANOSUKE, SUZUKI YASUTOSHI, TAKEDA HAZIMU, SEKINE OSAMU, USUDA YOSHIMARU, SASAHARA KUNIHIRO
• Format: Journal Article
• Language: Japanese
• Published: Japanese Society of Chemotherapy 1982; 公益社団法人 日本化学療法学会
• ISSN: 0009-3165; 1884-5894
• DOI: 10.11250/chemotherapy1953.30.880

Single 75mg doses of netilmicin, were administered once intramuscularly to 3 healthy volunteersand 9 hospitalized patients suffering from various degrees of renal disfunction with creatinine clearance(Ccr) from 1.6 to 104ml/min, and netilmicin levels in serum and urine were determined by bioassay, and pharmacokinetic analysis were performed by the one component open model.The maximum serum level of netilmicin(Cmax) obtained from the mean serum level in the volunteers was 4.6μg/ml, the half life in serum(t1/2) was 1.77 hrs, body serum clearance(CLB) was 81.4ml/min, and renal clearance (CLR) was 75.3ml/min.The MICs of netilmicin tested clinically isolated pathogenic bacteria in Japan and the duration of the effective levels of netilmicin in serum, which was calculated from the simulated netilmicin serum levels using the pharmacokinetic parameters obtained, were compared. As the result, it was found that the following dosage regimen was established: 75 mg of netilmicin is administered every 12 hrs for the infectious disease with S. aureus, and every 8 to 12 hrs for the infectious disease with the gram negative bacilli. Repeated administration of 75 mg of netilmicin in every 8 hrs would not induce any adverse reactions.As renal function decreased, CLR was decreased. The mean CLR and t1/2 in 3 patients with a creatinine clearance below 10ml/min. were 2.0-3.0ml/min. and 22.9hrs. respectively. The relationship between the elimination rate constant(Kel) and Ccr was expressed as Kel=0.0043 Ccr-0.0006. The calculated nomogram of netilmicin for the initial dose and maintenance dose in patients with various degrees of renal insufficiency, when netilmicin is administered every 8 hrs and 12 hrs, was obtained.Serum levels in 6 subject, and urinary levels in 3 subjects were determined by radioimmunoassays (RIA) as well as by bioassays, and the both were well correlated, the correlation coefficients being 0.943 and 0.990, respectively. It may suggested that RIA method is considered to be a rapid assay method to determine the serum level of netilmicin. 健康成人志願者3名と, クレアチニンクリアランス (Ccr) L6-104ml/minの種々の程度の腎機能を有する入院患者9名, 計12名にNetilmicin 75mgを1回筋注した際の血中, 尿中濃度をBioassayによって測定し, Onecompartmentopenmode1によって薬動力学的解析を加えた.健康成人志願者の平均血清中濃度から求めた最高値 (Cmax) は4.6μg/ml, 血中濃度半減期 (t1/2) は1.77時間, Body clearance (CLB) は81.4ml/min, Renal clearance (CLB) 1よ75.3ml/minであった.わが国における各種臨床分離細菌に対するNetilmicinのMIC分布と, 薬動力学的パラメーターから求めた血清中濃度推移より計算した有効血清中濃度持続時間を比較し, S. aureus感染症には75mgを12時間間隔, グラム陰性桿菌感染症には8-12時間間隔使用が有効性が高く, 75mgの8時間間隔反復使用時の安全性にも, 問題は少ないと思われた.腎機能障害が進展するにつれてCLRは減少し, Ccr10ml/min以下の3例ではCLRは2.0-3.3ml/min, t1/2は22.88時間となり, 消失速度定数 (Kel) とCcrの間にはKel=0.0043・Ccr-0.0006の1次相関がみられ, 8時間, および12時間間隔で使用する際の腎機能に応じた維持量の計算図表を作成した.6症例35検体の血清中濃度と3症例9検体の尿中濃度はBioassayとともにRadioimmunoおsay (RIA) でも測定したが, 両測定値の間にはそれぞれ相関係数0.943と0.990の高い相関がみられ, Netilmicin使用中の血清中濃度を点検するためのRapid assayとしてRIA法は有用と考えられた.