Answers

1. C. The AUC (area under the curve) best describes the overall exposure of a person to a given drug over the course of the dosing interval. It describes the concentration of drug integrated over the period assessed, usually the dosing interval. A (Cmax) is not correct, as Cmax gives the maximum concentration achieved but does not reveal how long measurable concentrations of the drug were present or how long until this concentration was achieved. B (Tmax) only refers to the time until the maximum concentration is achieved, again not giving a reference to overall exposure over time. D (half-life) simply describes how much time is required for the concentration to decrease by one-half. Finally, clearance (E) is the volume of fluid (usually plasma) from which drug can be removed per unit of time and as such does not define exposure.

2. B. Clearance is defined as the volume of fluid from which drug is completely removed per unit of time and as such is a measure of the body's ability to remove drug by whatever manner (e.g., elimination, metabolism, excretion). Distribution is the theoretical volume to which the drug distributes and metabolism and excretion are simply methods of clearing drug.

3. D. Approximately five half-lives are required for a drug to reach steady-state concentrations. Since piroxicam has a half-life of 40 hours, it will require approximately 200 hours before steady state is reached. If given every 24 hours, shortly after the 8th dose (192 hours at exactly the 8th dose) steady state will be reached.

4. A. Drugs with a higher degree of plasma protein binding in general have a lower volume of distribution, since the plasma proteins (and thus the drug bound to the plasma protein) tend to stay in the plasma and not distribute to the extravascular tissues. Different drugs can have widely disparate volumes of distribution, so B is incorrect. Tissue binding of drugs is extremely important to drug distribution and can override plasma protein binding, so C is incorrect. Finally, D is incorrect, since in general the more lipophilic a drug is, the greater volume of distribution it has.

5. C. Bioavailability describes the portion of the drug that reaches the systemic circulation without being metabolized or eliminated. Bioavailability is highly dependent on the drug and the route of administration. Cmax (B) is incorrect, since this is only the maximum concentration reached following a dose and gives no measure of the amount reaching the circulation. The other terms (ideal dose and theoretical dose) are fabricated.

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