The Food Effect

Most orally administered pharmaceutical products are somewhat water soluble. These drugs enter the small intestines and are absorbed. Depending on their solubility, they can be fully or partially absorbed and enter systemic circulation after liver metabolism. However, the path followed by lipophilic drug substances is different. When small amounts of lipids (or fats) are ingested they enter the small intestines and are not soluble. Fats require the generation of bile, created in the pancreas, to mix with them to form small particles called micelles. These small “balloon-like” particles entrap both the intact fat and specific enzymes that interact to break the lipids down into smaller molecules called free fatty acids. Free fatty acids are readily soluble while intact fats (normally ingested as a triglyceride or ethyl esters) are not.

When a single capsule of a lipophilic drug is ingested, there simply isn’t enough fat present to encourage the gall bladder to contract and push bile into the intestines. The drug remains intact and may have no efficacy and worse, may cause intestinal issues that can further result in compliance problems. To overcome this, most lipophilic drugs require being taken with food, and in many cases, a fatty meal. In this way, bile is produced as a result of the higher level of fat entering the small intestines, and the lipophilic drug is entrapped in the micelle formed by the interaction of the excreted bile and fatty food.

To circumvent the problem of absorption without a fatty meal, ALT™ is encapsulated with the lipophilic drug into a soft gelatin capsule. When the capsule opens in the stomach and passes into the small intestines the mixture self-micellizes and entraps both enzymes and lipids. Free fatty acids are formed as a result of this interaction and immediately absorbed into the outer layer of cells of the small intestines. These free fatty acids are re-esterified within the intestine into triglycerides, combined with various proteins to form small particles called chylomicrons and enter the lymphatic system where they travel directly to cells throughout the body or to the liver for metabolism. Chylomicrons are the primary particles that carry lipids to the liver where they are converted to VLDL, LDL and HDL particles.
When the lipid is also a drug substance, the use of ALT enables their efficient absorption with or without food.