Clinical Pharmacokinetics

Question 1

Phase I

Answer 1

Reduction, oxidation, hydrolysis with CYPp450 systems(1A2, 2C9, C19, 2D6, 34A)

Question 2

Phase II

Answer 2

Conjugation

Flucuronidation, acetylation, sulfation (GAS)

Question 3

Factors affecting elimination

Answer 3

Age (renal function, creatinine from muscle)
Disease states (acute renal failure, chronic renal failure)
Hemodialysis/hemofiltration (may filter out drugs, hydrophilic drugs, small molecular weight)
Medications (competition for elimination pathways, potential for enhanced toxicity)

Question 4

Population pharmacokinetics (PK)

Answer 4

Derived from clinical trials (healthy adults)
Averages of parameter for the population
Remember: not all patients are textbook cases

Question 5

PK variations in neonates

Answer 5

Immature skin so increased skin hydration, increased absorption of topical products (thats why no sunscreen for babies under 6 mo)
Increased ECF, larger Vd for liquid-soluble
Metabolic pathways mature at different times
GFR and tubular secretion/reabsorption immature at birth

Question 6

PK variations in elderly

Answer 6

Skin thinning, thus increased absorption of topical products
Increased adipose tissue, increase Vd of fat soluble drugs
Decreased ECF, decreased Vd of liquid soluble drugs
Decreased GFR

Question 7

Why is being at steady state important?

Answer 7

Minimizes potential for over/under dose adjustment
Ensures maximum and stable distribution
Safe and potentially cost effective dose adjustments

Question 8

Drug interactions

Answer 8

Absorption: Drug A affects Drug B, chelation, pH changes
Distribution: binding site competition (albumin), disease state alteration in plasma proteins, fluid status, adipose
Metabolism: hepatic, cyp450 enzymes (inductions,inhibition)
Elimination: competition for pathways, primarily renal

Question 9

CrCl

Answer 9

Creatinine clearance

Normal is 70