Читать книгу Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulations - Sheila Annie Peters - Страница 35

In principle, a drug or a prodrug may be metabolized to the active metabolite in more than one site. For example, an active metabolite of an orally administered drug/prodrug may be formed in the gut and in the liver. In addition, metabolites other than the active metabolite may be formed in parallel at both sites. The active metabolite may be eliminated in the gut and liver before entry into liver. For the simplest case of a single metabolite formed solely in liver, following IV administration of the parent, under first‐order, linear kinetic conditions, the rate of change in the amount of metabolite (A_M ), in systemic circulation is given by:

(1.50)

k_f,M and k_el,M are the first‐order rate constants of metabolite formation (strictly, metabolite entry into systemic circulation) and elimination respectively. For simplicity, the metabolic pathway leading to the active metabolite is the only elimination pathway for the parent drug and a complete release of the metabolite into systemic circulation without prior elimination in the organ where it is formed is assumed.