Profile likelihood-based confidence intervals using Monte Carlo integration for population pharmacokinetic parameters.
Population pharmacokinetic (PPK) analysis usually employs nonlinear mixed effects models using first-order linearization methods. It is well known that linearization methods do not always perform well in actual situations. To avoid linearization, the Monte Carlo integration method has been proposed. Moreover, we generally utilize asymptotic confidence intervals for PPK parameters based on Fisher information. It is known that likelihood-based confidence intervals are more accurate than those from the usual asymptotic confidence intervals. We propose profile likelihood-based confidence intervals using Monte Carlo integration. We have evaluated the performance of the proposed method through a simulation study, and analyzed the erythropoietin concentration data set by the method.
Clinical Research Coordination Department, Chugai Pharmaceutical Co., Ltd., Chuo-ku Tokyo, Japan. funatogawatks@chugai-pharm.co.jp
Takashi
T
Funatogawa
Ikuko
I
Funatogawa
Akifumi
A
Yafune
D003198:Computer Simulation; D016001:Confidence Intervals; D004921:Erythropoietin / Q000493:pharmacokinetics; D006801:Humans; D016013:Likelihood Functions; D015233:Models, Statistical; D009010:Monte Carlo Method; D010599:Pharmacokinetics; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D004921:Erythropoietin