Nonlinear PK

Question 1

Does drug concentration increase or decrease proportionally with dose?

Answer 1

Increase

Question 2

T or F: Dose-normalized conc profiles overlap each other for different dose groups

Answer 2

True

Question 3

How does the saturation of drug change at high doses?

Answer 3

At high doses,
* The drug conc at a time point is higher than the expected levels from linear kinetics
* The PK parameters for the rate of drug elimination reflect slower rates (longer half-life, lower CL)

Question 4

How does Phenytoin affect the saturation?

Answer 4

• Used as an anticonvulsant/antiepileptic
• Adm orally in single/divided doses of 200 to 400 mg/day
• Narrow therapeutic index (therapeutic= 10-20 mg/L)
• CNS adverse effects that are conc-dependent
• The metabolic capacity is limited (Vmax: 7mg/kg/day, Km: 4 mg/L)

Question 5

What does high saturation at higher doses mean for elimination?

Answer 5

Slower elimination

Question 6

What happens to dicloxacillin CLr when renal secretion is saturated?

Answer 6

Decrease

Question 7

When is plasma protein binding saturable?

Answer 7

at higher doses