药物非房室模型分析课件.pptVIP

NONCOMPARTMENTAL ANALYSIS;GENERAL PRINCIPLES OF STATISTICAL MOMENTS;Examples of Statistical Moment Usage;In statistics, the mean is a measure of a sample mean and is actually an estimate of the true population mean. In pharmacokinetics, we can calculate the moment of the theoretical probability density function (i.e., the solution of a differential equation describing the plasma concentration time data), or we can calculate moments from measured plasma concentration-time data. These curves are referred to as sample moments and are estimates of the true curves. ;Assume a theoretical relationship of C(t) as a function of time. The non-normalized moments, Sr , about the origin are calculated as:;Non-normalized moments Kinetic parameter;From: Rowland M, Tozer TN. Clinical Pharmacokinetics – Concepts and Applications, 3rd edition, Williams and Wilkins, 1995, p. 487.;Normalized moments Kinetic parameter;AREA DETERMINATION;B. Numerical Integration;B. Numerical Integration;B. Numerical Integration;;B. Numerical Integration;B. Numerical Integration;B. Numerical Integration;;Time (hr) C (mg/L) 0 2.55 1 2.00 3 1.13 5 0.70 7 0.43 10 0.20 18 0.025;;CLEARANCE CONCEPTS;Rate In = QCa;Extraction Ratio: Ratio of the rate of xenobiotic elimination and the rate at which xenobiotic enters the organ.;Clearance: The volume of blood from which all of the drug would appear to be removed per unit time.;Relationship between CL Q;Total Clearance;Total Clearance;Additivity of clearance;Exception: sig. pulmonary elimination;100 mg drug administered to a volunteer resulted in 10 mg excreted in urine unchanged:;Application of Clearance Concepts;Application of Clearance Concepts;Mechanisms of altered elimination;STEADY-STATE VOLUME OF DISTRIBUTION;Cf;At steady-state:;Simplifying:;Using blood concentrations:;Calculation via moment analysis:;If administration via a short term inf