7 - Kinetics - Volume

Question 1

Distribution of a drug depends on…

Answer 1

• Drug properties
• Plasma protein binding
• Disease state/age

Question 1

Define VD

Answer 1

Volume of distribution/ Constant for any drug in average healthy person.
VD = Total drug absorbed/plasma drug concentration.
E.g. 100mg injection with 98mg staying in the blood means low VD as not much as distributed to the tissue.

Question 2

1) How does VD depend on lipophilicity?
2) What about protein binding?
3) What about MW?

Answer 2

1) More lipophilic = more crosses blood capillary barrier and into tissue = higher VD
2) Higher protein binding = less leave to get to tissue = lower VD
3) Higher MW = harder to leave blood = lower VD

Question 3

1) What can VD be used to calculate?
2) If VD of a drug = 40L and Conc. needed in plasma = 20mg/L, calculate.
3) What if F = 0.25, how much to give orally?

Answer 3

1) Loading Dose (LD)
2) c=mV, m=cV = 20mg/L x 40L = 800mg
3) 800/0.25 = 3200mg

Question 4

How can diseases or age affect VD?

Answer 4

Age can decrease plasma protein amounts -> less protein binding -> more VD
Diseases can do either e.g. decreasing protein amounts or increasing capillary permeability

Question 5

How does VD affect
1) Time to reach steady state
2) steady state concentration
3) elimination rate

Answer 5

Doesn’t affect actual steady state concentration. Affects rest.

Question 6

1) At steady state, rate of drug admininstration is lower/equal/higher than drug elimination rate.
2) CSS is calculated as…
3) What effect does higher VD have on steady state?
4) What effect does increasing LD have on steady state?
5) Purpose of LD?

Answer 6

1) Equal
2) Maintenance dose rate (MDR)/CL
3) Increase VD = increase time to reach CSS
4) Increase Loading Dose (LD) = decrease time to reach CSS
5) Reach steady state quicker.

Question 7

What’s CL? (in pharmacokinetics)

Answer 7

Clearance is amount of drug irreversibly removed from body per unit time. Not same as drug elimination rate (ke)

Question 8

Describe overall renal clearance process
- What’s GFR?

Answer 8

Filtrated via glomerular capillaries into bowman’s capsule, reabsorbed via peritubular capillaries along with secretions from capillaries, and excreted out.

• Glomerular Filtration Rate = total volume of filtrate produced by all nephrons per unit time.

Question 9

Describe the liver when it comes to clearance

Answer 9

Liver – Recirculate some drugs where they are absorbed and travel to liver and then conjugated so it releases back into gut. Then deconjugated in gut and reabsorbed and cycle can repeat.

Question 10

1) LD =
2) MDR =
Q:
1) 2mg/min is given and CSS = 3mg/L, what’s CL?
2) What would happen to CSS if GFR lowered so CL halved?

Answer 10

1) LD = Desired CSS x VD
2) MDR = CSS x CL. Generally, dose is given at every half-life.

We know MDR = 2mg/min and CSS = 3mg/L,
MDR = CSS x CL, CL = MDR/CSS = (2mg/min)/(3mg/L) = 0.667L/min
2) If CL halved, and MDR stayed the same,
CSS = MDR/CL = (2mg/min)/(0.667/2 L/min) = (2mg/min)/(0.333L/min) = 6mg/L. CSS has doubled.