Phamacokinetics 1: Bioavailability, Vd, and Clearance Flashcards
bioavailability
-the fraction of drug absorbed systemically after administration
IV bioavailability
-100%
F
fractional bioavailability
-calculating this value depends onknowing the plasma concentrations achieved when that drug is administered intravenously
=AUCoral/AUCintravenous
bioavailability and generic drugs
- 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
volume of distribution
- 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
calculating Vd
- amount of drug in the body/ concentration of drug in a reference compartment
- drug dose/plasma concentration
loading dose (DL)
(Vd x Cp)/F
-F does not make a difference if bioavailability is 100%
clearance (Q)
- 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
elimination equation
clearance x Cp
-this also gives us the maintenance dose rate
how to take bioavailability into consideration when calculating elimination rate/maintenance dose rate
(Cl/F) x Cp
whole body clearance =
- dose/area under the curve
2. Vd x k (this is a rearrangement of the formula for half life
Plasma concentration at steady state (Cpss)
(Dose rate x F)/Cl
possible reasons for low F values
- poor absorption
- pre systemic extraction (first pass)
- efflux transport (P glycoproteins)
Cmax
peak plasma concentrtion following a dose
Tmax
time of peak plasma concentration following a dose
AUC
area under the curves, extent of absorption
reasons to perform therapeutic drug monitoring
- narrow therapeutic window
- relationship between safety/efficacy and Cp
- unpredictable dose response relationship
- reliable assay exists
zero order administration
- do not confuse with zero order clearance
- this is a constant amount of drug adminstered over time
loading dose
- 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
routes of clearance
- metabolic, typically through the liver and some GI mucosa
- renal filtration
if a drug is completely cleared by the kidney, what is not produced?
-a metabolite
assessment of kidney function
-why is this important
- 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
First order elimination
- elimination rate
- clearance
- fraction eliminated
- frequency
- 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
zero order elimination
- 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)
when do drugs act like zero order and first order
- 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
time to steady state
-what will it impact
- 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
if you double the infusion rate of a drug that is eliminated in a first order fashion…
- 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
how does a single dose in a two compartment model look on a semi log graph
-distribution from plasma to tissues appears bi-phasic on a semi log scale
pharmacokinetic drug interactions
- absorption (binding/chelation vs pH related)
- distribution (protein binding)
- metabolism (induction vs inhibition)
- other interactions of clearance (renal tubular secretion)
aminoglycoside kinetics
- absorption
- distribution
- metabolism
- excretion
- absorption: not absorbed orally
- distribution: poor lipid solubility, little protein binding, Vd usually around 0.3 L/kg
- metabolism: none
- excretion: renal
succinylchoilne and pharmacogenomics
-when given to patients with BChE deficiency it produces a prolonged neurmuscular block
isoniazid and pharmacogenetics
-based on acetylation status of the patient and can produced neurotoxicity
animalarials and pharmacogenomics
If the patient has G6PD
