Predicting Food Effects on Oral Extended-Release Drug Products: A Retrospective Evaluation

AbstractTheoretically, the risk of food effects for extended-release (ER) products compared to IR products may be less because: (1) postprandial physiological changes are usually transient and last for 2 –3 h only; and (2) the percentage of drug release from an ER product within the first 2–3 h post dose is usually small under both fasted and fed states. The major postprandial physiological changes that can affect oral absorption of ER drugs are delayed gastric emptying and prolonged intestina l transit. Oral absorption of ER drugs under fasted state mainly occurs in large intestine (colon and rectum) while the absorption of ER drugs under fed state occurs in both small and large intestines. We hypothesized that food effects for ER products are mainly caused by intestinal region-dependent absorption and food intake is more likely to increase rather than decrease the exposure of ER products due to a longer transit time and improved absorption in small intestine. For drugs with good absorption from large intestine, food effects on the area under the curve (AUC) of ER products are usua lly not expected. Our survey of oral drugs approved by the US FDA between 1998–2021 identified 136 oral ER drug products. Among the 136 ER drug products, 31, 6 and 99 products exhibited increased, decreased, and unchanged AUC under fed conditions, respectively. In general, when an ER product exhib its a fasted bioavailability (BA) relative to its corresponding immediate-release (IR) produc...
Source: The AAPS Journal - Category: Drugs & Pharmacology Source Type: research