03-02-2025 | Commentary
Solubility-Limited Absorption Identified by a Simplified PBPK Model for the Prediction of Positive Food Effect for BCS II/IV Drugs
Published in: Clinical Pharmacokinetics
Login to get accessExcerpt
Multiple factors in the gut can influence absorption of orally administered drugs. These include gastric emptying, transit in the small intestine, dissolution, solubilization by bile salts, absorption, gut metabolism, and transporter-mediated efflux [1]. Dissolution is also influenced by solubility, drug formulation, and gastric pH, while absorption depends on drug permeability and splanchnic blood flow [2]. Food can influence each of these processes, leading to a positive or negative food effect (FE) through changes in plasma concentration of drugs, thereby impacting the onset and duration of the therapeutic effect [3‐5]. The net impact of food on the absorption of drugs depends on the physiological mechanisms it influences and the solubility/permeability of drugs, according to the biopharmaceutical classification system (BCS) classes of compounds [6] (Fig. 1).
Fig. 1
Impact of food-induced physiological mechanisms for BCS drugs. BCS biopharmaceutical classification system; PPI proton pump inhibitor; GI gastrointestinal; GIT gastrointestinal tract. In column 1, change “Reduce luminal drug concentration leads to increase susceptibility of substrates to intestinal efflux” to “Reduced luminal drug concentration leads to increased susceptibility of substrates to intestinal efflux”. In column 5 change “Increase extent of adsorption proportional to logP (fenofibrate, alectinib, danazol)” to “Increased extent of adsorption proportional to logP (fenofibrate, alectinib, danazol)”. In column 5, change “Increase rate of adsorption (phenytoin)” to “Increased rate of adsorption (phenytoin)”
×
…