Introduction to ADME

Question 1

When given a concentration vs time curve, where would onset, duration and intensity of pharmacologic effect be located?

Answer 1

Onset - Onset occurs when the drug reaches the minimally effective concentration. “how quickly the drug exhibits its pharmacologic effect”

Duration - The duration lasts as long as the drug remains above the minimally effective concentration. “how long it exhibits its effects”

Intensity - The intensity of effect is determined by the maximal concentration of the drug achieved and when that maximum concentration is achieved. “the magnitude of its pharmacologic”

Question 2

When given a route of administration, what are the barriers that may reduce the amount of drug that reaches the site of action?

Answer 2

Barriers include membranes that limit the movement of drug into certain tissues, as well as enzymes within membranes that can metabolize the parent drug.

Question 3

Define the terms disposition, pharmacokinetics and pharmacodynamics.

Answer 3

Disposition - The fate of a drug once it enters the systemic circulation

Pharmacokinetics - The study of absorption, distribution, biotransformation and elimination of xenobiotics. “how the body acts on the drug”

Pharmacodynamics - The study of the molecular, biochemical and physiological effects of xenobiotics and their mechanisms of action. “how the drug acts on the body”

Question 4

What is the current percent of drugs that fail in clinical trials due to ADME problems?

Answer 4

In the past, 40% of drugs failed in clinical trials due to ADME. Currently, due to an improved preclinical ADME assessment, less that 10% of drugs fail clinical trials due to ADME.

Question 5

What are the primary routes of administration?

Answer 5

4 broad categories.

Ingestion (high variability)
- gastrointestinal tract
Inhalation
- lungs
Dermal
- skin
Parenteral
-intravenous
-subcutaneous
-intramuscular
-intraperitoneal

Question 6

What are the 4 consequences of drug metabolism (biotransformation) as it relates to pharmacologic activity?

Answer 6

Dependent on if the parent and/or metabolite are pharmacologically active.

1. Active drug to inactive metabolite
2. Active drug to active metabolite
3. Inactive drug to active metabolite
4. Active drug to reactive metabolite