Population pharmacokinetics of teicoplanin in infants and children
We analyzed teicoplanin (TEIC) pharmacokinetics in infants and children using the nonlinear mixed effects model (NONMEM) to estimate population pharmacokinetics parameters. Subjects were 63 children (28 days to 16 years old) prescribed TEIC at Kitasato University Hospital and undergoing therapeutic...
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Published in | Japanese Journal of Chemotherapy Vol. 55; no. 1; pp. 17 - 22 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | Japanese |
Published |
Japanese Society of Chemotherapy
01.01.2007
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/chemotherapy1995.55.17 |
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Abstract | We analyzed teicoplanin (TEIC) pharmacokinetics in infants and children using the nonlinear mixed effects model (NONMEM) to estimate population pharmacokinetics parameters. Subjects were 63 children (28 days to 16 years old) prescribed TEIC at Kitasato University Hospital and undergoing therapeutic drug monitoring. Population pharmacokinetics parameters were calculated using 1-compartment model of clearance (CLTEIC) and volume of distribution (VdTEIC). An exponential error model was used to determine interindividual variability and a relative error model for residual variability. Patient age, gender, weight, serum creatinine, and serum albumin were covariates. The observed TEIC serum concentration was 101 points ranging from 4.4-39.1ug/mL. TEIC population pharmacokinetics parameters finally estimated were: CLTEIC=0.00836×(wt/Scr) 0786 (L/h) and VdTEIC=0.8× wt (L). Interindividual variability was CLTEIC=26.7 (%) and VdTEIC=32.7 (%), and residual variability was 2.8, μg/mL. CLTEIC changes due to aging correlated well with that of kidney gravity. Model validity was sufficient. Our reports suggest that the population parameters are useful in evaluating TEIC pharmacokinetics in children undergoing long-term hospitalization. |
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AbstractList | We analyzed teicoplanin (TEIC) pharmacokinetics in infants and children using the nonlinear mixed effects model (NONMEM) to estimate population pharmacokinetics parameters. Subjects were 63 children (28 days to 16 years old) prescribed TEIC at Kitasato University Hospital and undergoing therapeutic drug monitoring. Population pharmacokinetics parameters were calculated using 1-compartment model of clearance (CLTEIC) and volume of distribution (VdTEIC). An exponential error model was used to determine interindividual variability and a relative error model for residual variability. Patient age, gender, weight, serum creatinine, and serum albumin were covariates. The observed TEIC serum concentration was 101 points ranging from 4.4-39.1ug/mL. TEIC population pharmacokinetics parameters finally estimated were: CLTEIC=0.00836×(wt/Scr) 0786 (L/h) and VdTEIC=0.8× wt (L). Interindividual variability was CLTEIC=26.7 (%) and VdTEIC=32.7 (%), and residual variability was 2.8, μg/mL. CLTEIC changes due to aging correlated well with that of kidney gravity. Model validity was sufficient. Our reports suggest that the population parameters are useful in evaluating TEIC pharmacokinetics in children undergoing long-term hospitalization. We analyzed teicoplanin (TEIC) pharmacokinetics in infants and children using the nonlinear mixed effects model (NONMEM) to estimate population pharmacokinetics parameters. Subjects were 63 children (28 days to 16 years old) prescribed TEIC at Kitasato University Hospital and undergoing therapeutic drug monitoring. Population pharmacokinetics parameters were calculated using 1-compartment model of clearance (CLTEIC) and volume of distribution (VdTEIC). An exponential error model was used to determine interindividual variability and a relative error model for residual variability. Patient age, gender, weight, serum creatinine, and serum albumin were covariates. The observed TEIC serum concentration was 101 points ranging from 4.4-39.1ug/mL. TEIC population pharmacokinetics parameters finally estimated were: CLTEIC=0.00836×(wt/Scr) 0786 (L/h) and VdTEIC=0.8× wt (L). Interindividual variability was CLTEIC=26.7 (%) and VdTEIC=32.7 (%), and residual variability was 2.8, μg/mL. CLTEIC changes due to aging correlated well with that of kidney gravity. Model validity was sufficient. Our reports suggest that the population parameters are useful in evaluating TEIC pharmacokinetics in children undergoing long-term hospitalization. 乳児期から小児期におけるteicoplanin (TEIC) の母集団薬物動態を, 非線形混合効果モデル (Nonlinear Mixed Effects Model: NONMEM) を用いて解析した。対象は, 北里大学病院にてTEICが投与され, therapeutic drug monitoring (TDM) が実施された患児63例 (28日齢~16歳) とした。母集団パラメータの算出は, クリアランス (CLTEIC), 分布容積 (VdTEIC) を薬物動態パラメータとし, 1-コンパートメントモデルを適用した。個体間変動は指数誤差モデルを, 残差変動は相対誤差モデルを使用した。TEIC薬物動態の解析には, 年齢 (Age), 性別 (Gender), 体重 (wt), 血清クレアチニン値 (Scr), 血清アルブミン値 (Alb) を共変量候補として検討した。測定された血漿中TEIC濃度 (111ポイント) は, 4.4~39.1μg/mLであった。最終的に次の母集団薬物動態パラメータが得られた。CLTEIC=0.00836× (wt/Scr) 0786 (L/hr) VdTEIC=0.81×wt (L)個体問変動は, CLTEIC;26.7%, VdTEIC;32.7%, 残差変動は2.8μg/mLであった。CLTEICは, 腎重量の発育推移によく近似しており, 小児期の腎機能の発育を反映していることが示唆された。モデルバリデーションの結果は良好であり, 長期入院患児を中心とした小児のTEIC薬物動態評価に有用であると考えられた。 |
Author | Kobayashi, Masahiro Ishii, Masahiro Kimura, Toshimi Sunakawa, Keisuke Arima, Misayo Yago, Kazuo |
Author_FL | 小林 昌宏 矢後 和夫 砂川 慶介 有馬 三佐代 木村 利美 石井 正浩 |
Author_FL_xml | – sequence: 1 fullname: 小林 昌宏 – sequence: 2 fullname: 有馬 三佐代 – sequence: 3 fullname: 木村 利美 – sequence: 4 fullname: 石井 正浩 – sequence: 5 fullname: 矢後 和夫 – sequence: 6 fullname: 砂川 慶介 |
Author_xml | – sequence: 1 fullname: Ishii, Masahiro organization: Department of Pediatrics, School of Medicine, Kitasato University – sequence: 1 fullname: Arima, Misayo organization: Department of Pharmacy, Kitasato University Hospital – sequence: 1 fullname: Sunakawa, Keisuke organization: Department of Infectious Disease, School of Medicine, Kitasato University – sequence: 1 fullname: Kobayashi, Masahiro organization: Department of Pharmacy, Kitasato University Hospital – sequence: 1 fullname: Kimura, Toshimi organization: Department of Pharmacy, Kitasato University Hospital – sequence: 1 fullname: Yago, Kazuo organization: Department of Pharmacy, Kitasato University Hospital |
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References | 6) Terragna A, Ferrea G, Loy A, Danese A, Bernareggi A, Cavenaghi L, et al: Pharmacokinetics of teicoplanin in pediatric patients. Antimicrob Agents Chemother 1988; 32: 1223-6 10) Maxwell G M. Principles of pediatric pharmacology. Oxford University Press, New York, 1984; p.6 2) Sheiner L B, Rosenberg B, Melmon K L: Modeling of individual pharmacokinetics for computer aided drug dosage. Comp Biomed Res 1972; 5: 411-59 3) Ette E I: Stability and performance of a population pharmacokinetic model. J Clin Pharmacol 1997; 37: 486-95 8) Schwartz G J, Brion L P, Spitzer A: The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am 1987; 34: 571-90 1) Beal S L, Sheiner L B: The NONMEM system. Am Stat 1980; 34: 118-9 4) 中山貴美子, 源馬均, 貝原徳紀, 丹羽俊朗: 成人におけるteicoplaninの母集団薬物動態解析.日化療会 誌 2006; 54: 2-6 7) Armenian S H, Singh J, Arrieta A C: Risk factors for mortality resulting from bloodstream infections in a pediatric intensive care unit. Pediatr Infect Dis J 2005; 24: 309-14 9) Leger F, Bouissou F, Coulais Y, Tafani M, Chatelut E: Estimation of glomerular filtration rate in children. Pediatr Nephrol 2002; 17: 903-7 5) Tarral E, Jehl F, Tarral A, Simeoni U, Monteil H, Willard D, et al: Pharmacokinetics of teicoplanin in children. J Antimicrob Chemother 1988; 21 (Suppl A): 47-51 |
References_xml | – reference: 3) Ette E I: Stability and performance of a population pharmacokinetic model. J Clin Pharmacol 1997; 37: 486-95 – reference: 9) Leger F, Bouissou F, Coulais Y, Tafani M, Chatelut E: Estimation of glomerular filtration rate in children. Pediatr Nephrol 2002; 17: 903-7 – reference: 4) 中山貴美子, 源馬均, 貝原徳紀, 丹羽俊朗: 成人におけるteicoplaninの母集団薬物動態解析.日化療会 誌 2006; 54: 2-6 – reference: 1) Beal S L, Sheiner L B: The NONMEM system. Am Stat 1980; 34: 118-9 – reference: 2) Sheiner L B, Rosenberg B, Melmon K L: Modeling of individual pharmacokinetics for computer aided drug dosage. Comp Biomed Res 1972; 5: 411-59 – reference: 10) Maxwell G M. Principles of pediatric pharmacology. Oxford University Press, New York, 1984; p.6 – reference: 7) Armenian S H, Singh J, Arrieta A C: Risk factors for mortality resulting from bloodstream infections in a pediatric intensive care unit. Pediatr Infect Dis J 2005; 24: 309-14 – reference: 8) Schwartz G J, Brion L P, Spitzer A: The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am 1987; 34: 571-90 – reference: 5) Tarral E, Jehl F, Tarral A, Simeoni U, Monteil H, Willard D, et al: Pharmacokinetics of teicoplanin in children. J Antimicrob Chemother 1988; 21 (Suppl A): 47-51 – reference: 6) Terragna A, Ferrea G, Loy A, Danese A, Bernareggi A, Cavenaghi L, et al: Pharmacokinetics of teicoplanin in pediatric patients. Antimicrob Agents Chemother 1988; 32: 1223-6 |
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Title | Population pharmacokinetics of teicoplanin in infants and children |
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