Pharmacokinetics

Question 1

What is the fundamental hypothesis of pharmacokinetics?

Answer 1

There is a predictable relationship b/t plasma (or serum) concentration of a drug and its effect

Question 2

Rate of elimination equation

Answer 2

Rate = (Vmax * C) / (Km + C)

Question 3

WRT elimination, if the system is not saturated, what happens with increasing concentration?

Answer 3

increasing concentration increases elimination

Question 4

Absolute rate

Answer 4

mg/hr

changes as drug concentration changes

Question 5

Fractional rate

Answer 5

fraction/hr

stays constant

Question 6

First assumption for models

Answer 6

Elimination must be first order

Question 7

Second assumption of models

Answer 7

instant distribution

Question 8

What happens as steady state?

Answer 8

rate in = rate out

dose/dose interval = elimination/dose interval

Question 9

What are the primary pharmacokinetic parameters?

Answer 9

Volume of distribution
Clearance
Bioavailablity

Question 10

What pharmacokinetic parameters are derived?

Answer 10

half-life

Ke

Question 11

Volume of distribution

Answer 11

Volume of a sample fluid required to explain dilution of dose given

Vd = dose / concentration at time zero

Question 12

What are some causes of non-uniform distribution of solutions WRT Vd?

Answer 12

1. Ion trapping - i.e. weak bases accumulate inside cells
2. protein binding in plasma
3. tissue: plasma partition coefficients

Question 13

What adjustments can be made WRT Vd?

Answer 13

1. For “ideal body weight” – e.g. obese patients would not follow typical formula
2. Pathologic conditions – e.g. edema, ascites

Question 14

Clearance (Definition and equation)

Answer 14

Clearance is the virtual volume that is freed of drug per unit time

CL (L/hr) = Rate of absolute elimination (mg/hr) / conc. (mg/L)

Question 15

Clearance - calculation using dose

Answer 15

CL (L/hr) = Dose (mg) / AUC (mg*hr/L)

AUC = area under the curve

Question 16

Extraction Ratio (definition, #, equation)

Answer 16

Most direct measure of organ function

# 0-1
Varies with functional state of organ

ER = (Cin - Cout) / Cin

Question 17

Clearance - calculation using ER

Answer 17

CL (L/hr) = ER * Blood flow (L/hr)

Question 18

Ke - elimination rate constant

Answer 18

The fraction of drug that is removed per hr

Ke = CL / Vd

Question 19

Half life equation

Answer 19

t_1/2 = 0.693 / Ke

Question 20

Bioavailability (F)

Answer 20

FRACTION of drug administered that reaches the CENTRAL CIRCULATION

F = f * (1 - ER)
f ~ 1.0 – its the fraction absorbed into portal circulation

Question 21

Accumulation vs Elimination

Answer 21

The time it takes to accumulate to steady state is the same time it take to eliminate the drug

Both of these are determined using half life

5 half lives accumulates/eliminates 97% of final/total

Question 22

Accumulation Factor (Ra)

Answer 22

Ra = 1 / (fraction lost in one dosing interval)

Question 23

Fraction remaining equation

Answer 23

e^(-Ke * T)

T = dose interval

Question 24

Estimated concentration after the first dose is administered

Answer 24

Cp(0) = F * D / Vd

Question 25

Dosing rate (calculation)

Answer 25

CL * Css

Question 26

Calculation for adjusting dosing regimen based on actual effect of first dose

Answer 26

New Rate = Old Rate * (Desired Css / Measured Css)

(mg/hr) (mg/hr) (mg/L) (mg/L)

Question 27

Loading dose (equation + use)

Answer 27

Loading dose = Vd * Target concentration

Used when you need to reach the peak quickly

Question 28

Concentration equation for a one-compartment model

-Assumptions

Answer 28

Cp(t) = A * (e^(-Ke * t))

Assumptions

• Must be first order process
• Body ONE homogenous compartment
• instantaneous mixing

Question 29

Equations for Css(max) and Css(min)

Answer 29

Css(max) = (F * D / Vd) * Ra

Css(min) = Css(max) * Fraction remaining at T