Extremely lipid-soluble drugs can enter the lymphatic system directly and may avoid first-pass metabolism. Which statement best reflects this?

• A. They are always absorbed into the hepatic portal vein before reaching systemic circulation.
• B. They can enter lymphatics directly and may bypass first-pass metabolism.
• C. They cannot be absorbed without entering the bloodstream first.
• D. They require active transport to reach the lymphatics.

Answer: (B)

Extremely lipid-soluble drugs can reach systemic circulation via the intestinal lymphatic system, bypassing the liver’s first-pass metabolism. In the intestine, very lipophilic drugs can be incorporated into chylomicrons along with dietary lipids. These chylomicrons are too large for blood capillaries, so they travel through the lymphatic vessels, pass into the thoracic duct, and then drain into the bloodstream near the subclavian vein. Because this route avoids the hepatic portal vein on the first pass, the drug can escape substantial hepatic metabolism before reaching systemic circulation. This pathway is facilitated by high lipid solubility and is enhanced by lipid-containing meals that promote chylomicron formation.

So the statement that best reflects this is that extremely lipid-soluble drugs can enter lymphatics directly and may bypass first-pass metabolism. This is not about always going through the portal vein, and these drugs do not require active transport to reach the lymphatics; absorption is largely driven by lipid solubility and diffusion into the lymphatic system.