PK解析の基礎—Phase Iを中心に—

抄録

We describe fundamental knowledge of pharmacokinetics analysis for phase I trials, particularly focusing on basic parameters (such as bioavailability, volume of distribution, fraction unbound, clearance), estimation and analysis methods (such as compartmental and non-compartmental), points to consider (such as steady state and dose proportionality). The NCA is an abbreviation for Non Compartmental Analysis, and the meaning is pharmacokinetic analysis without pharmacokinetic model. There is something that we should consider in NCA such as AUC calculation method, handling method of not detectable concentrations, point selection for λz calculation, and selection of sampling time. Steady state occurs when the overall intake of a drug is equilibrium with its elimination. At steady state the mean plasma concentrations of the drug are similar by any dosing interval. In practice, it is generally considered that steady state is reached when a time of 5 times the half-life for a drug. For the dose proportionality, the measures of exposure, such as maximal blood concentration (C_max), area under the curve from 0 to infinity (AUC), are proportional to the dose. The three methods, Analysis of variance of the PK response, normalized by dose, linear regression and power model, are used to assess dose proportionality.