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신생아에서 Amikacin의 집단약동학
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저자명
윤영란,신종범,손지홍,박지영,임은주,김혜리,정원석,김철호,이순용,차인준,신재국,Yoon. Young-Ran,Shin. Jong-Beom,Shon. Ji-Hong,Park. Ji-Young,Rim. Eun-Ju,Kim. Hye-Ri
간행물명
臨床藥理學會誌= The journal of Korean Society for Clinical Pharmacology and Therapeutics
권/호정보
2000년|8권 2호|pp.232-247 (16 pages)
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대한임상약리학회
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
서지반출

기타언어초록

Background: Population pharmacokinetics of amikacin were analyzed to evaluate the relationship between its pharmacokinetic characteristics and clinical covariates in Korean neonates and to provide initial dosage regimen according to the pathophysiological characteristics of each patients as well as to provide the population parameters required for Bayesian approach in TDM. Methods : 314 steady-state amikacin plasma concentrations were obtained from 157 Korean neonates with a mean postconceptional age (PCA) of $38.1{pm}4.1$ weeks and mean postnatal age (PNA) of $10.4{pm}11.2$ days. All subjects were classified to group A (PCA<33 weeks, n=25), group B $(33;weeks{leq}PCA<37;weeks,;n=35)$ and group C (PCA>37 weeks, n=97) according to their PCA. The individual pharmacokinetic parameters of serum amikacin concentrations were analyzed from one-compartment model in each subject. The population model employed assumes the existence of residual variability in the serum concentrations and interindividual variability in the pharmacokinetic parameters. The effects of demographic variables on the clearance(Cl), volume of distribution(Vd) of amikacin were evaluated from multiple nonlinear regression using $NOMEN^{circledR}$. Results : Peak concentration/dose ratio was higher in group A than in group Band C. PCA and 5-min Apgar score were good predictive variables of the Cl, body weight was a good variable to determine the Cl and the Vd of amikacin in neonates. From the best fitted pharmacokinetic model, the population average Cl was 0.103 L/kg/h and was reduced in neonates with $33{leq}PCA>37$ weeks $({ imes}0.633)$, whit PCA<37 weeks $({ imes}0.588)$, with PCA<33 weeks and with 5-min Apgar score <7 $({ imes}0.752)$. The population average Vd was estimated to 0.626 L/kg. The inter-individual variability for Cl and Vd were 24.5 % and <5 %, respectively. Residual variability was estimated to 12.3 %. Conclusions : Amikacin pharmacokinetics of neonates seems to be influenced by PCA and 5-min Apgar score as well as body weight. From the population pharmacokinetic parameters, we predicted the priori dose regimen to achieve desired concentrations within the therapeutic range in Korean neonates.