Population pharmacokinetics of biapenem in patients and healthy subjects
Population pharmacokinetic parameters of biapenem (BIPM), a carbapenem antibiotic, were generated by a nonlinear mixed effects model using the NONMEM program based on plasma concentrations in patients and healthy subjects. A total of 384 plasma samples were collected from 66 subjects, and their demo...
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| Published in | Japanese Journal of Chemotherapy Vol. 54; no. 1; pp. 7 - 17 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
Japanese Society of Chemotherapy
01.01.2006
公益社団法人 日本化学療法学会 |
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| Online Access | Get full text |
| ISSN | 1340-7007 1884-5886 |
| DOI | 10.11250/chemotherapy1995.54.7 |
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| Abstract | Population pharmacokinetic parameters of biapenem (BIPM), a carbapenem antibiotic, were generated by a nonlinear mixed effects model using the NONMEM program based on plasma concentrations in patients and healthy subjects. A total of 384 plasma samples were collected from 66 subjects, and their demographic background data were recorded. The data obtained were analyzed using the two-compartment model. The covariates (age, weight [Wt], creatinine clearance [Ccr]) and one factor (the effect of disease) were tested for an effect on the pharmacokinetics of BIPM. Population pharmacokinetic parameters were not related to the effect of disease. Total clearance (CL) was found to be associated with Ccr, and the volume of distribution of the central compartment (V1) was associated with Wt. The volume of distributionof the peripheral compartment (V2) was not associated with Wt. The final formulae for the population mean parameters were: CL=0.0720×Ccr+3.04 (L/h), V1=0.0990×Wt (L), inter-compartmental clearance (Q)=13.5 (L/h), V2=7.00 (L).The validity of the model has been evaluated by the bootstrapping method. The time above the MIC's (T>MIC) were estimated from the plasma concentration profiles calculated based on population mean parameters and MICe s in order to create tables for establishment of dosing regimens for BIPM. |
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| AbstractList | Population pharmacokinetic parameters of biapenem (BIPM), a carbapenem antibiotic, were generated by a nonlinear mixed effects model using the NONMEM program based on plasma concentrations in patients and healthy subjects. A total of 384 plasma samples were collected from 66 subjects, and their demographic background data were recorded. The data obtained were analyzed using the two-compartment model. The covariates (age, weight [Wt], creatinine clearance [Ccr]) and one factor (the effect of disease) were tested for an effect on the pharmacokinetics of BIPM. Population pharmacokinetic parameters were not related to the effect of disease. Total clearance (CL) was found to be associated with Ccr, and the volume of distribution of the central compartment (V1) was associated with Wt. The volume of distributionof the peripheral compartment (V2) was not associated with Wt. The final formulae for the population mean parameters were: CL=0.0720×Ccr+3.04 (L/h), V1=0.0990×Wt (L), inter-compartmental clearance (Q)=13.5 (L/h), V2=7.00 (L).The validity of the model has been evaluated by the bootstrapping method. The time above the MIC's (T>MIC) were estimated from the plasma concentration profiles calculated based on population mean parameters and MICe s in order to create tables for establishment of dosing regimens for BIPM. Population pharmacokinetic parameters of biapenem (BIPM), a carbapenem antibiotic, were generated by a nonlinear mixed effects model using the NONMEM program based on plasma concentrations in patients and healthy subjects. A total of 384 plasma samples were collected from 66 subjects, and their demographic background data were recorded. The data obtained were analyzed using the two-compartment model. The covariates (age, weight [Wt], creatinine clearance [Ccr]) and one factor (the effect of disease) were tested for an effect on the pharmacokinetics of BIPM. Population pharmacokinetic parameters were not related to the effect of disease. Total clearance (CL) was found to be associated with Ccr, and the volume of distribution of the central compartment (V1) was associated with Wt. The volume of distributionof the peripheral compartment (V2) was not associated with Wt. The final formulae for the population mean parameters were: CL=0.0720×Ccr+3.04 (L/h), V1=0.0990×Wt (L), inter-compartmental clearance (Q)=13.5 (L/h), V2=7.00 (L).The validity of the model has been evaluated by the bootstrapping method. The time above the MIC's (T>MIC) were estimated from the plasma concentration profiles calculated based on population mean parameters and MICe s in order to create tables for establishment of dosing regimens for BIPM. 成人感染症患者等および健康成人において得られたカルバペネム系薬biapenem (BIPM) の血漿中濃度を, Nonlinear Mixed Effects Model (NONMEM) を用いて解析し, 母集団薬物動態パラメータを算出した。解析には, 成人感染症患者等および健康成人の計66例, 384ポイントの血漿中濃度および患者背景を用いた。薬物動態モデルとしては点滴静注時の2-コンパートメントモデルを使用し, BIPMの薬物動態に影響を与える共変量として年齢 (Age), 体重 (Wt), およびクレアチニン・クリアランス (Ccr), ならびに因子として薬物動態に対する疾患の有無の影響を検討した。その結果, 全身クリアランス (CL) にはCcrの, 体循環血コンパートメントの分布容積 (V1) にはWtの影響が認められた。末梢循環血コンパートメントの分布容積 (V2) にはWtの影響は見出されなかった。これらの結果をふまえて母集団薬物動態解析を行った結果, BIPMの母集団平均パラメータはCL=0.0720×Ccr+3.04 (L/h), V1=0.0990×Wt (L), 体循環血コンパートメントと末梢循環血コンパートメントの間の移行クリアランス (Q) 313.5 (L/h), V2=7.00 (L) であった。内部バリデーション法の一つであるBootstrap法によって, モデルバリデーションを行った結果, 確立したモデルは妥当であると考えられた。また, 求めた母集団平均パラメータよりシミュレーションした血漿中濃度推移およびMICを用いて, 種々の想定患者背景におけるTime above MIC (T>MIC)(%) を推定し, BIPMの投与設計を考案するうえでの一助となる一覧表を作成した。 |
| Author | Shibutani, Sachiyo Sato, Nobuo Tanaka, Yukari Shibasaki, Shigeki |
| Author_FL | 佐藤 信雄 田中 由香利 渋谷 幸代 芝崎 茂樹 |
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| References | 16) 斎藤玲, 三浦敏明, 多羅尾史明: Biapenemの体内動態に関する研究.Chemotberapy 42 (Suppl 4): 277-284, 1994 4) 原耕平, 松本文夫, 河田幸道, 他: 各種感染症に対するbiapenemの臨床的検討.JPn J Antibiot 52: 629-660, 1999 10) 青木信樹, 薄田芳丸, 甲田豊: Biapenemの腎障害患者における体内動態および臨床成績.Chemotherapy 42 (Suppl 4): 350-364, 1994 2) Hikida M, Kawashima K, Nishiki K, et al: Renal dehydropeptidase-I stability of LJC 10,627, a new carbapenem antibiotic. Antimicrob Agents Chemother 36: 481-483, 1992 6) Craig W A: Pharmacokinetic/pharmacodynamic parameters: Rationale for antibacterial dosing of mice and men. Clinical Infectious Dis 26: 1-12, 1998 26) 平田純生: 効くはずの抗菌薬が効かない? 薬局 56: 123-133, 2005 25) 佐藤玲子, 谷川原祐介: 抗菌薬のPK/PD.医薬ジヤーナル 41: 67-74, 2005 9) 本田芳宏, 斉藤純一, 中井祐之: Biapenemのin vitro抗菌力, 喀痰内移行, 肺組織移行および呼吸器感染症での使用経験.Chemotherapy 42 (Suppl 4): 301-313, 1994 15) 横山隆児玉節, 竹末芳生: 外科領域におけるbiapenemの基礎的, 臨床的検討.Chemotherapy 42 (Suppl 4): 549-558, 1994 24) 辻彰: 3.4分布容積.わかりやすい生物薬剤学 (第2版), p.88-91, 廣川書店, 東京, 1997 12) 田中日出和, 岩井重富, 佐藤毅; 外科領域におけるbiapenemの基礎的, 臨床的検討.Chemotherapy 42 (Suppl 4): 506-512, 1994 5) Craig W A: Interrelationship between pharmacokinetics and pharmacodynamics in determining dosage regimens for broad-spectrum cephalosporins. Diagn Microbiol Infect Dis 22: 89-96, 1995 8) Takata T, Aizawa K, Shimizu A, et al: Optimization of dose and dose regimen of biapenem based on pharmacokinetic and pharmacodynamic analysis. J Infection Chemother 10: 76-85, 2004 3) Kozawa O, Uematsu T, Matsuno H, et al: Pharmacokinetics and safety of a new parenteral carbapenem antibiotic, biapenem (L-627), in elderly subjects. Antimicrob Agents Chemother 42: 1433-1436, 1998 20) 家入一郎, 魚井徹, 大和田栄治: 第2節2赤池の情報量基準AIC.薬物血中濃度モニタリングのためのPopulation Pharmacokinetics入門 (堀了平監修, 緒方宏泰, 奥村勝彦編), p.69-70. 薬業時報社, 東京, 1988 11) 那須勝, 後藤陽一郎, 山崎透: カルバペネム系抗生物質biapenemの基礎的研究および呼吸器感染症に対する臨床的検肘. Chemotherapy 42 (SUppl 4); 418-425, 1994 1) 吉田益史, 渡邊正人, 三橋進: 新規カルバペネム系抗生物質biapenemの細菌学的評価.Chemotherapy 42 (Suppl4): 1-19, 1994 17) 木村丹, 松島敏春, 田野吉彦: Biapenemの胸水中移行に関する検討.Chemotherapy 42 (Suppl 4): 285-289, 1994 19) Cockcroft D W, Gault M H: Prediction of creatinine clearance from serum creatinine. Nephron 16: 31-41, 1976 13) 由良二郎, 品川長夫, 石川周: 外科領域におけるbiapenemの基礎的, 臨床的検討.Chemotherapy 42 (Suppl 4): 513-522, 1994 23) 柴孝也, 前沢浩美, 吉田正樹: Biapenemの基礎的・臨床的検討.Chemotherapy 42 (Suppl 4): 322-328, 1994 7) Andes D, Craig W A: Animal model pharmacokinetics and pharmacodynamics: a critical review. International Journal of Antimicrobial Agents 19: 261-268, 2002 18) 保田仁介, 山元貴雄, 岡田弘二: 産婦人科領域におけるBiapenemの基礎的, 臨床的検討.Chemotherapy 42 (Suppl 4): 583-590, 1994 22) 山下憲昭, 河島浩輔, 野村和外: Biapenemの各種実験動物における体内動態.Chemotherapy 42 (Suppl 4): 243-250, 1994 21) John P, Nicholas H, Bruce G, et al: A procedure for generating bootstrap samples for the validation of nonlinear mixed-effects population models. Cornputer methods and programs in biomedicine 59: 19-29, 1999 14) 森本健, 木下樽明, 中谷守一: 新規全合成carbapenem, biapenemの外科臨床泊験.Chemotherapy 42 (Suppl 4): 535-548, 1994 |
| References_xml | – reference: 24) 辻彰: 3.4分布容積.わかりやすい生物薬剤学 (第2版), p.88-91, 廣川書店, 東京, 1997 – reference: 26) 平田純生: 効くはずの抗菌薬が効かない? 薬局 56: 123-133, 2005 – reference: 1) 吉田益史, 渡邊正人, 三橋進: 新規カルバペネム系抗生物質biapenemの細菌学的評価.Chemotherapy 42 (Suppl4): 1-19, 1994 – reference: 10) 青木信樹, 薄田芳丸, 甲田豊: Biapenemの腎障害患者における体内動態および臨床成績.Chemotherapy 42 (Suppl 4): 350-364, 1994 – reference: 17) 木村丹, 松島敏春, 田野吉彦: Biapenemの胸水中移行に関する検討.Chemotherapy 42 (Suppl 4): 285-289, 1994 – reference: 23) 柴孝也, 前沢浩美, 吉田正樹: Biapenemの基礎的・臨床的検討.Chemotherapy 42 (Suppl 4): 322-328, 1994 – reference: 6) Craig W A: Pharmacokinetic/pharmacodynamic parameters: Rationale for antibacterial dosing of mice and men. Clinical Infectious Dis 26: 1-12, 1998 – reference: 12) 田中日出和, 岩井重富, 佐藤毅; 外科領域におけるbiapenemの基礎的, 臨床的検討.Chemotherapy 42 (Suppl 4): 506-512, 1994 – reference: 11) 那須勝, 後藤陽一郎, 山崎透: カルバペネム系抗生物質biapenemの基礎的研究および呼吸器感染症に対する臨床的検肘. Chemotherapy 42 (SUppl 4); 418-425, 1994 – reference: 7) Andes D, Craig W A: Animal model pharmacokinetics and pharmacodynamics: a critical review. International Journal of Antimicrobial Agents 19: 261-268, 2002 – reference: 19) Cockcroft D W, Gault M H: Prediction of creatinine clearance from serum creatinine. Nephron 16: 31-41, 1976 – reference: 9) 本田芳宏, 斉藤純一, 中井祐之: Biapenemのin vitro抗菌力, 喀痰内移行, 肺組織移行および呼吸器感染症での使用経験.Chemotherapy 42 (Suppl 4): 301-313, 1994 – reference: 3) Kozawa O, Uematsu T, Matsuno H, et al: Pharmacokinetics and safety of a new parenteral carbapenem antibiotic, biapenem (L-627), in elderly subjects. Antimicrob Agents Chemother 42: 1433-1436, 1998 – reference: 21) John P, Nicholas H, Bruce G, et al: A procedure for generating bootstrap samples for the validation of nonlinear mixed-effects population models. Cornputer methods and programs in biomedicine 59: 19-29, 1999 – reference: 8) Takata T, Aizawa K, Shimizu A, et al: Optimization of dose and dose regimen of biapenem based on pharmacokinetic and pharmacodynamic analysis. J Infection Chemother 10: 76-85, 2004 – reference: 15) 横山隆児玉節, 竹末芳生: 外科領域におけるbiapenemの基礎的, 臨床的検討.Chemotherapy 42 (Suppl 4): 549-558, 1994 – reference: 18) 保田仁介, 山元貴雄, 岡田弘二: 産婦人科領域におけるBiapenemの基礎的, 臨床的検討.Chemotherapy 42 (Suppl 4): 583-590, 1994 – reference: 14) 森本健, 木下樽明, 中谷守一: 新規全合成carbapenem, biapenemの外科臨床泊験.Chemotherapy 42 (Suppl 4): 535-548, 1994 – reference: 20) 家入一郎, 魚井徹, 大和田栄治: 第2節2赤池の情報量基準AIC.薬物血中濃度モニタリングのためのPopulation Pharmacokinetics入門 (堀了平監修, 緒方宏泰, 奥村勝彦編), p.69-70. 薬業時報社, 東京, 1988 – reference: 13) 由良二郎, 品川長夫, 石川周: 外科領域におけるbiapenemの基礎的, 臨床的検討.Chemotherapy 42 (Suppl 4): 513-522, 1994 – reference: 22) 山下憲昭, 河島浩輔, 野村和外: Biapenemの各種実験動物における体内動態.Chemotherapy 42 (Suppl 4): 243-250, 1994 – reference: 4) 原耕平, 松本文夫, 河田幸道, 他: 各種感染症に対するbiapenemの臨床的検討.JPn J Antibiot 52: 629-660, 1999 – reference: 25) 佐藤玲子, 谷川原祐介: 抗菌薬のPK/PD.医薬ジヤーナル 41: 67-74, 2005 – reference: 2) Hikida M, Kawashima K, Nishiki K, et al: Renal dehydropeptidase-I stability of LJC 10,627, a new carbapenem antibiotic. Antimicrob Agents Chemother 36: 481-483, 1992 – reference: 5) Craig W A: Interrelationship between pharmacokinetics and pharmacodynamics in determining dosage regimens for broad-spectrum cephalosporins. Diagn Microbiol Infect Dis 22: 89-96, 1995 – reference: 16) 斎藤玲, 三浦敏明, 多羅尾史明: Biapenemの体内動態に関する研究.Chemotberapy 42 (Suppl 4): 277-284, 1994 |
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| Title | Population pharmacokinetics of biapenem in patients and healthy subjects |
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