Which of the following statements about drug metabolism in pharmacokinetics is correct?

A. Drugs with strong first-pass metabolism are best administered via an enteral route: Drugs that undergo extensive first-pass metabolism are often less effective when given enterally, as much of the drug is inactivated by the liver before reaching systemic circulation. Non-enteral routes (e.g., sublingual, IV) are preferred to bypass the liver initially. B. Metabolism alters medications so that they can be excreted from the body: The liver uses enzymatic processes to convert drugs into more water-soluble forms, facilitating their elimination through the kidneys or bile. This process can either activate, inactivate, or detoxify substances depending on the drug. C. The first-pass effect increases the bioavailability of orally administered drugs: The first-pass effect reduces, not increases, the bioavailability of orally administered drugs. It refers to the initial metabolism in the liver that significantly reduces the active concentration of a drug before it reaches systemic circulation. D. Metabolism primarily occurs in the kidneys: While the kidneys are essential for drug excretion, metabolism primarily occurs in the liver. Hepatic enzymes, especially those of the cytochrome P-450 system, play the central role in drug biotransformation.