药代动力学Ch-2-PK-EC.pptVIP

* * * * * Relationship Between Absorption, Distribution, and Elimination（2） Pharmacokinetics ＆ pharmacodynamics vs time Peak of Pharmacological effects, adverse effects (Peak concentration) * * * * * * * * * * Pharmacokinetic Studies. Key Measurements. To investigate the bioequivalence of 2 drug products or compounds, the FDA considers PK studies that determine the area under the concentration-time curve (AUC), maximum concentration (Cmax), and time to Cmax (Tmax) for the study compound (generic) and a reference compound (innovator).1 Each of these values for the study compound are compared with those of the reference compound. For the study and reference compounds to be considered bioequivalent, their rates and extents of absorption must not show a significant difference when administered at the same molar dose of the therapeutic ingredient under similar experimental conditions. The red area in the diagram represents the AUC, or the extent of absorption, of the reference compound. The yellow area represents the AUC of the study compound. Cmax is an indicator of the absorption rate and Tmax is influenced by the route of compound administration. A difference of greater than 20% in Cmax or the AUC represents a significant difference between the study and reference compounds. Reference 1. Approved Drug Products With Therapeutic Equivalence Evaluations. 23rd ed. 2003. FDA/CDER Web site. Available at: /cder/ob/docs/preface/ecpreface.htm#Therapeutic Equivalence-Related Terms. Accessed September 29, 2003. * * * * * * * * * * * * * * * * * Phase II (Synthetic or Conjugation结合) Reactions A. usually require energy, nearly always inactivates parent compound , with few exception. B. Phase II reactions are conjugation reactions. In humans, glucuronidation is the most important one. C. The conjugation reactions frequently occur after an initial Phase I reaction. The reaction is to make the drug more polar, and more