The Korean Journal of Applied Statistics (응용통계연구)

The Korean Statistical Society (한국통계학회)
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Estimation Methods for Population Pharmacokinetic Models using Stochastic Sampling Approach

확률적 표본추출 방법을 이용한 집단 약동학 모형의 추정과 검증에 관한 고찰

  • 김광희 (이화여자대학교 통계학과) ;
  • 윤정화 (이화여자대학교 통계학과) ;
  • 이은경 (이화여자대학교 통계학과)
  • Received : 2015.03.05
  • Accepted : 2015.03.30
  • Published : 2015.04.30
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Abstract

This study is about estimation methods for the population pharmacokinetic and pharmacodymic model. This is a nonlinear mixed effect model, and it is difficult to find estimates of parameters because of nonlinearity. In this study, we examined theoretical background of various estimation methods provided by NONMEM, which is the most widely used software in the pharmacometrics area. We focused on estimation methods using a stochastic sampling approach - IMP, IMPMAP, SAEM and BAYES. The SAEM method showed the best performance among methods, and IMPMAP and BAYES methods showed slightly less performance than SAEM. The major obstacle to a stochastic sampling approach is the running time to find solution. We propose new approach to find more precise initial values using an ITS method to shorten the running time.

본 논문에서는 집단 약동/약력학 모형 추정을 위한 다양한 추정방법들을 이론적으로 비교, 분석하였다. 특히 확률적 표본을 이용한 방법들인 IMP, IMPMAP, SAEM 방법과 베이지안 방법의 이론적 배경과 이들의 성능을 자세히 살펴보고, 기존의 선형근사를 이용한 FO, FOCE 등의 방법과 비교 분석하였다. 확률적 표본을 이용한 추정방법들이 추정에 많은 시간이 소요된다는 문제점을 개선하기 위하여 좀 더 좋은 초기치를 찾는 방안으로 상대적으로 짧은 시간에 정확한 추정치를 계산해주는 ITS 방법을 이용하였다.

Keywords

References

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