Phamacokinetics 1: Bioavailability, Vd, and Clearance

Question 1

bioavailability

Answer 1

-the fraction of drug absorbed systemically after administration

Question 2

IV bioavailability

Answer 2

-100%

Question 3

F

Answer 3

fractional bioavailability
-calculating this value depends onknowing the plasma concentrations achieved when that drug is administered intravenously
=AUCoral/AUCintravenous

Question 4

bioavailability and generic drugs

Answer 4

• this is what is tested when comparing generic drugs being prepared for the market and name brand drugs
• must exhibit a similar rate and extent of absorption
• for approval, AUC, Tmax, and Cmax are all taken into consideration

Question 5

volume of distribution

Answer 5

• proportionality constant that relates amount of drug in the body to the amount of drug in the plasma
• this is not a real number, this is hypothetical
• the more lipophilic a drug is, the wider its distribution will be
• valuable for calculating a loading dose that will achieve a desired serum concentration

Question 6

calculating Vd

Answer 6

1. amount of drug in the body/ concentration of drug in a reference compartment
2. drug dose/plasma concentration

Question 7

loading dose (DL)

Answer 7

(Vd x Cp)/F

-F does not make a difference if bioavailability is 100%

Question 8

clearance (Q)

Answer 8

• quantitative capacity for the body to remove a drug from a certain amount of fluid over time (v
• accomplished by a clearing organ and limited by the blood flow to that organ

Question 9

elimination equation

Answer 9

clearance x Cp

-this also gives us the maintenance dose rate

Question 10

how to take bioavailability into consideration when calculating elimination rate/maintenance dose rate

Answer 10

(Cl/F) x Cp

Question 11

whole body clearance =

Answer 11

1. dose/area under the curve

2. Vd x k (this is a rearrangement of the formula for half life

Question 12

Plasma concentration at steady state (Cpss)

Answer 12

(Dose rate x F)/Cl

Question 13

possible reasons for low F values

Answer 13

• poor absorption
• pre systemic extraction (first pass)
• efflux transport (P glycoproteins)

Question 14

Cmax

Answer 14

peak plasma concentrtion following a dose

Question 15

Tmax

Answer 15

time of peak plasma concentration following a dose

Question 16

AUC

Answer 16

area under the curves, extent of absorption

Question 17

reasons to perform therapeutic drug monitoring

Answer 17

• narrow therapeutic window
• relationship between safety/efficacy and Cp
• unpredictable dose response relationship
• reliable assay exists

Question 18

zero order administration

Answer 18

• do not confuse with zero order clearance

- this is a constant amount of drug adminstered over time

Question 19

loading dose

Answer 19

• necessary when it takes a long time for a drug to reach a desired concentration when administered in a zero order fashion
• can be calculated by multiplying Vd with the desired Cp
• does not change the half life or the time it takes to get to steady state

Question 20

routes of clearance

Answer 20

• metabolic, typically through the liver and some GI mucosa

- renal filtration

Question 21

if a drug is completely cleared by the kidney, what is not produced?

Answer 21

-a metabolite

Question 22

assessment of kidney function

-why is this important

Answer 22

• 24 hour creatinine collections
• or estimated based on Scr plus other variables
• cockroft and gault equation to estimate GFR
• if you are not clearing from your kidney, the drug could remain in the body longer and have an increased affect, therefore you want to adjust the dose based on kidney function

Question 23

First order elimination

• elimination rate
• clearance
• fraction eliminated
• frequency

Answer 23

• elimination rate is proportional to concentration
• clearance is independent of Cp and is constant
• fraction eliminated per unit time is constant
• this is applicable to most drugs

Question 24

zero order elimination

Answer 24

• elimination rate is constant and independent of Cp
• clearance is dependent on Cp
• constant amount of eliminated drug per unit time
• applicable to few drugs (booze)

Question 25

when do drugs act like zero order and first order

Answer 25

- act like first order when the concentration is much lower than the Km - act like zero order when the substrate is much higher than Km

Question 26

time to steady state | -what will it impact

Answer 26

- typically requires about 3-5 half lives - will impact the times that blood levels are drawn and whether or not a loading dose is needed - independent of the desired concentration

Question 27

if you double the infusion rate of a drug that is eliminated in a first order fashion...

Answer 27

- the steady state concentration doubles as well - this is the same for double the dose and keeping the rate the same - they are directly proportional

Question 28

how does a single dose in a two compartment model look on a semi log graph

Answer 28

-distribution from plasma to tissues appears bi-phasic on a semi log scale

Question 29

pharmacokinetic drug interactions

Answer 29

- absorption (binding/chelation vs pH related) - distribution (protein binding) - metabolism (induction vs inhibition) - other interactions of clearance (renal tubular secretion)

Question 30

aminoglycoside kinetics - absorption - distribution - metabolism - excretion

Answer 30

- absorption: not absorbed orally - distribution: poor lipid solubility, little protein binding, Vd usually around 0.3 L/kg - metabolism: none - excretion: renal

Question 31

succinylchoilne and pharmacogenomics

Answer 31

-when given to patients with BChE deficiency it produces a prolonged neurmuscular block

Question 32

isoniazid and pharmacogenetics

Answer 32

-based on acetylation status of the patient and can produced neurotoxicity

Question 33

animalarials and pharmacogenomics

Answer 33

If the patient has G6PD