Shaoyao Gancao Decoction (SGD) derived from Zhang Zhongjing’s “Typhoid Theory” is composed of peony and licorice, having the efficacy of nourishing liver, relaxing spasm, and relieving pain. Modern compatibility studies of SGD on chemistry, pharmacology, and pharmacokinetics all demonstrate the reasonable compatibility of peony and licorice. However, the present research on pharmacokinetics is only descriptive and limited to the influence onin vivodynamic process of certain ingredients; correspondingly, there is lack of studies on the essence of these efficacious substances’in vivochanges; that is, whether it is because there existsin vivodrug interaction in absorption, distribution, metabolism, and excretion (ADME) of active ingredients that leads to the improvement of bioavailability. We herein take SGD as an example and suggest that it is necessary to studyin vivodrug interaction of main efficacious components mediated by metabolic enzymes, transport proteins, or plasma protein binding in the course of ADME, which is helpful to illustrate the principle of pharmacokinetic compatibility from the essence leading to the changes of effective substancesin vivo.