1. C. The primary site of absorption is the small intestine. Because of its large surface area and high blood perfusion rate, the small intestine is optimal for absorbing drugs. Some drug absorption occurs in the stomach and large intestine, but because of their reduced surface area in relative terms and for some drugs less than optimal physicochemical conditions, these tissues play a lesser role in drug absorption. Because of the tissue type, very little drug absorption occurs through the esophagus.

2. E. To be approved, generic formulations must exhibit the same rate and extent of absorption as the trademark compound. All of the other choices can affect drug absorption. For example, slowing gastric emptying time may increase the absorption of a drug absorbed in the stomach. Alterations in gastric motility may affect the amount of time a drug spends in the region of the gastrointestinal tract, where it undergoes the most extensive absorption. The presence of food may cause decreased absorption through binding to the drug or may increase absorption through making a better local environment for absorption of particular drugs. Finally, changes in drug formulation can alter absorption by changing dissolution rates.

3. B. P-glycoprotein transporters in the intestinal lumen serve as an efflux transporter for many drugs. This transporter pumps drugs out of the enterocytes into which they were absorbed and back into the intestinal lumen, reducing absorption. Facilitated diffusion and pinocytosis generally result in drug influx (absorption). The cytochrome P450 3A enzymes metabolize drugs; therefore, even though they may reduce the amount of drug absorbed, the reduction is due to drug metabolism, not efflux transport back into the intestinal lumen.

4. A. Un-ionized drugs cross into the cerebrospinal fluid more readily than ionized drugs. All of the other choices are correct.

5. C. Lead can substitute for calcium in the bone crystal lattice, resulting in bone brittleness. Bone may become a reservoir for other substances as well. Several drugs, such as chlorpromazine, may accumulate in the eye. Drugs with extremely high lipid— water partition coefficients tend to accumulate in fat, while basic amines tend to accumulate in the lungs. Many agents bind avidly to albumin in the blood.

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