Quantitative pharmacokinetics

Question 1

what do you need to draw a concentration-time curve (oral)

Answer 1

Cmax - peak plasma concentration

Tmax - the time required to achieve Cmax

minimum toxic concentration (MTC)

minimum effective concentration (MEC

duration of action

Question 2

key pharmacological features of a conc.-time curve

Answer 2

therapeutic window - area between MTC and MEC

log scale or linear scale - straight or curved

Question 3

compare zero-order kinetics and first-order kinetics

Answer 3

first order refers to change by a constant fraction per unit time (e.g. 1/4/20min)
- most drugs are eliminated via first order upon first dose
- can change to zero order when drug conc. increases and saturation of metabolic pathways occurs

zero order refers to change by a constant amount per unit time (0.25mg/20min)

Question 4

provide a drug that follows zero-order elimination

Answer 4

ethanol follows zero order

• 7-10g per hour
• 1std drink is 10g

Question 5

describe a simple approach to determine total body clearance in noncompartmental analysis

Answer 5

1. administer a single dose of drug (i.v. bolus or oral)
2. collect blood samples and measure drug plasma concentration at defined time points
3. plot a plasma concentration-time curve, and calculate the AUC

Cltotal(L/hr) =dose (mg) ×F/AUC (mg ∙ hr/L)

Question 6

trapezoidal method to calculate area under the curve (AUC)

Answer 6

For one area (AUCt3−t4 =
C3 + C4 × (t4 − t3)/
2)

For whole area (AUC0−last = AUCt0−t1 + AUCt1−t2 + ⋯ + AUCt4−t(last)) or infonnite of calculatign with residuals

Question 7

describe drug bioavailability

Question 8

how does drug bioavailability help determine drug administration

Question 9

calculate C0

Answer 9

plasma concentration at time 0

Question 10

calculate total body clearance

Answer 10

Cltotal(L/hr) =
dose mg × F
AUC (mg ∙ hr/L)

Question 11

calculate volume of distribution

Answer 11

Vd (L) =
amount of drug in the body (mg)
/plasma concentration (mg/L)

Question 12

calculate elimination rate
constant

Answer 12

k (hr−1) =
Cltotal (L/hr)/
Vd (L)

Question 13

calculate elimination half-life

Answer 13

t1/2 =ln2/k = ln2 × Vd/
Cltotal

Question 14

describe steady-state concentration and its clinical relevance

Answer 14

steady-state concentration is the concentration of drug in the plasma reached when the rate of drug absorption is equal to the rate of drug elimination following repeated or continuous dosing

Question 15

clinical relevance of steady stance

Answer 15

higher doses and/or more frequent dosing will result in higher steady-state concentrations

to achieve clinical response rapidly: loading dose - high conc firstdose (= Vd × target plasma concentration) followed by smaller maintenance dose