Pharmacokinetics of pazufloxacin mesilate in patients with community-acquired pneumonia

We analyzed the concentration of pazufloxacin mesilate (PZFX) in the blood and evaluated its clinical effects. In seven patients (mean age: 71 years) with community-acquired pneumonia admitted and treated with PZFX. They experienced a total of eight episodes and their mean creatinine clearance was e...

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Published inJapanese Journal of Chemotherapy Vol. 56; no. 4; pp. 467 - 471
Main Authors Taguchi, Yoshio, Maniw, Ko, Abe, Noriyuki, Komatsu, Masaru
Format Journal Article
LanguageJapanese
Published Japanese Society of Chemotherapy 2008
公益社団法人 日本化学療法学会
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ISSN1340-7007
1884-5886
DOI10.11250/chemotherapy1995.56.467

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Abstract We analyzed the concentration of pazufloxacin mesilate (PZFX) in the blood and evaluated its clinical effects. In seven patients (mean age: 71 years) with community-acquired pneumonia admitted and treated with PZFX. They experienced a total of eight episodes and their mean creatinine clearance was estimated at 64.7±35.4 mL/min. An intravenous drip-infusion of 500 mg of PZFX alone during a period of 30 minutes was administered every 12 hours. Blood sampling for therapeutic drug monitoring were conducted on treatment day 3. On day 3 of PZFX administration, data on fever, symptoms, and white blood cell count were obtained to evaluate clinical effects. Assessment of the eight episodes showed T1/2β to be 2.87±1.02 hr, Cmax 30.39±12.18μg/mL, and AUC 67.89±27.87 hr·μg/mL. PZFX treatment was clinically effective in seven episodes (87.5%). Fever disappeared in less than three days in four cases and less than five days in three cases. Cmax and AUC in this study were 1.7 to 3.1 times greater than reported in the phase I clinical study and studies conducted on the elderly. Statistical data is thus required reflecting individual disposition to appropriately use an antimicrobial with due consideration for its pharmacokinetics/pharmacodynamics because the disposition of an antimicrobial containing PZFX differs with the patient.
AbstractList We analyzed the concentration of pazufloxacin mesilate (PZFX) in the blood and evaluated its clinical effects. In seven patients (mean age: 71 years) with community-acquired pneumonia admitted and treated with PZFX. They experienced a total of eight episodes and their mean creatinine clearance was estimated at 64.7±35.4 mL/min. An intravenous drip-infusion of 500 mg of PZFX alone during a period of 30 minutes was administered every 12 hours. Blood sampling for therapeutic drug monitoring were conducted on treatment day 3. On day 3 of PZFX administration, data on fever, symptoms, and white blood cell count were obtained to evaluate clinical effects. Assessment of the eight episodes showed T1/2β to be 2.87±1.02 hr, Cmax 30.39±12.18μg/mL, and AUC 67.89±27.87 hr·μg/mL. PZFX treatment was clinically effective in seven episodes (87.5%). Fever disappeared in less than three days in four cases and less than five days in three cases. Cmax and AUC in this study were 1.7 to 3.1 times greater than reported in the phase I clinical study and studies conducted on the elderly. Statistical data is thus required reflecting individual disposition to appropriately use an antimicrobial with due consideration for its pharmacokinetics/pharmacodynamics because the disposition of an antimicrobial containing PZFX differs with the patient.
We analyzed the concentration of pazufloxacin mesilate (PZFX) in the blood and evaluated its clinical effects. In seven patients (mean age: 71 years) with community-acquired pneumonia admitted and treated with PZFX. They experienced a total of eight episodes and their mean creatinine clearance was estimated at 64.7±35.4 mL/min.An intravenous drip-infusion of 500 mg of PZFX alone during a period of 30 minutes was administered every 12 hours. Blood sampling for therapeutic drug monitoring were conducted on treatment day 3. On day 3 of PZFX administration, data on fever, symptoms, and white blood cell count were obtained to evaluate clinical effects.Assessment of the eight episodes showed T1/2β to be 2.87±1.02 hr, Cmax 30.39±12.18μg/mL, and AUC 67.89±27.87 hr·μg/mL. PZFX treatment was clinically effective in seven episodes (87.5%). Fever disappeared in less than three days in four cases and less than five days in three cases.Cmax and AUC in this study were 1.7 to 3.1 times greater than reported in the phase I clinical study and studies conducted on the elderly.Statistical data is thus required reflecting individual disposition to appropriately use an antimicrobial with due consideration for its pharmacokinetics/pharmacodynamics because the disposition of an antimicrobial containing PZFX differs with the patient. 当院で2005年5月~2005年10月に入院した市中肺炎患者に対し, メシル酸バズフロキサシン (pazufloxacin mesilate, 以下PZFX) による治療を行った7症例, 8エピソード (男性6エピソード, 女性2エピソード, 平均年齢71歳, 平均推定クレアチニンクリアランス64.7±35.4mL/min) を対象に, PZFXの血中濃度解析と臨床効果について検討した。PZFXは単剤投与で500mgを12時間ごとに30分かけて点滴静注を行った。血中濃度測定用の採血は投与3日目に,(1) 投与直前 (2) 投与終了直前,(3) 投与開始1~1.5時間後,(4) 投与開始3~3.5時間後,(5) 投与開始5~5.5時間後の5ポイントで行った。また, 臨床効果は, PZFX投与3日目の発熱, 症状白血球数から評価した。結果, 8エピソードのT1/2β, CmaxおよびAUCの平均値は, それぞれ2.87±1.02hr, 30.39±12.18μg/mLおよび67.89±27.87hr・μg/mLであった。臨床効果は8エピソード中7エピソードが有効 (87.5%), 完全解熱までの期間は4例が3日以内, 3例が5日以内であった。本検討で算出されたCmaxおよびAUCは, 臨床第I相試験や高齢者を対象とした報告例と比較していずれも, およそ1.7~3.1倍程度高い値を示したが, これらは症例の腎機能, 基礎疾患等種々の病態が原因と考えられた。すなわち, PZFXを含む抗菌薬の体内動態は, 患者個々で変化するため, 抗菌薬のpharmacokinetics/pharmacodynamicsを考慮した適正使用のためには, 症例ごとの体内動態の算出が重要であると考えられた。
Author Komatsu, Masaru
Maniw, Ko
Taguchi, Yoshio
Abe, Noriyuki
Author_FL 阿部 教行
馬庭 厚
小松 方
田口 善
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  organization: Department of Clinical Pathology, Tenri Hospital
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References_xml – reference: 2) Forrest A, Nix D E, Ballow C H, Goss T F, Birmingham M C, Schentag J J: Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. Antimicrob Agents Chemother 1993; 37: 1073-81
– reference: 6) Fine M J, Auble T E, Yealy D M, Hanusa B H, Weissfeld L A, Singer D E, et al: A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 1997; 336: 243-50
– reference: 4) 阿部教行, 畑中徳子, 中村彰宏, 福田砂織, 松尾収二: カラムスイッチング法を用いた高速液体クロマトグラフィーによるPazufloxacinの血液中濃度測定法の確立. 医学検査 2007; 56: 1101-4
– reference: 9) 高木健三, 矢島洋一, 吉澤久雄: 高齢者における pazufloxacin注射薬の体内動態. 日本化学療法学会雑誌 2000; 48: 633-44
– reference: 3) 中島光好, 梅村和夫, 小菅和仁, 植松俊彦: Pazufloxacin注射薬の臨床第I相試験. 日本化学療法学会雑誌 1999; 47 (S-1) 141-75
– reference: 10) 青木信樹, 薄田芳丸, 石塚康夫, 若林信人, 林静一, 本間康夫, 他: Pazufloxacin注射薬の高齢者における体内動態. 日本化学療法学会雑誌 1999; 47 (S-1): 204-8
– reference: 7) Craig W A: Basic pharmacodynamics of antibacterials with clinical applications to the use of β-lactams, glycopeptides, and, linezolid. Infect Dis Clin N Am 2003; 17: 479-501
– reference: 5) Cockcroft D W, Gault M H: Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31-41
– reference: 1) Craig WA: Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis 1998; 26: 1-12
– reference: 8) Kuti J L, Horowitz S, Nightingale C H, Nicolau D P: Comparison of pharmacodynamic target attainment between healthy subjects and patients for ceftazidime and meropenem. Pharmacotherapy 2005; 25: 935-41
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Snippet We analyzed the concentration of pazufloxacin mesilate (PZFX) in the blood and evaluated its clinical effects. In seven patients (mean age: 71 years) with...
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SubjectTerms AUC
Cmax
community-acquired pneumonia
pazufloxacin mesilate
pharmacokinetics
Title Pharmacokinetics of pazufloxacin mesilate in patients with community-acquired pneumonia
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