Journal of Food Distribution Research Volume 30 Part 01 Page 0078
volume distribution
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Transcript of volume distribution
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Volume Distribution
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CONCEPT OF VOLUME OF DISTRIBUTION OF DRUGS:
DEFINITION OF VD
Add DRUG
to Beaker
Calculate Volume
Ota!" Sam#le
A$$a% &or 'Dru()
*St!r+
'Dru() , Amou"t Added Volume o& Beaker
Volume o& Beaker , Amou"t Added 'Dru()
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Distribution. ¿Where do drugs go?
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CONCEPT OF VOLUME OF DISTRIBUTION OF DRUGS:
DEFINITION OF VD
Do$e Bod%
-!t. DRUG
Calculate Volume
*T.!$ /olume !$ called VD
+
Ota!" Pla$ma Sam#le
A$$a% &or 'D)P
B% DEFINITION: VD , A0'D)P
*-.ere A !$ amou"t o& dru( !" od% a"d 'D)P !$ co"ce"trat!o" o& dru( !" #la$ma+
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Volume of distribution
Relative size of various
distribution volumeswithin a 70-kgindividual
• Interstitial fuid
represents about15% of the• total body weight.
• Intracellular fuid (fuid inside cells) -40% of
• the total bodyweight.
• Blood plasma - 8% of the body weight.
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lasma !ompartment
• Vd" around # $.
• Very high mole!ular
weight drugs% ordrugsthat bind to plasmaproteins e&!esively
• '&le" heparin ($ )*-#+
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'&tra!ellular ,uid
Vd" between (and ( $.
Drugs that havea low mole!ularweight but arehydrophili!.
'&le
tra!uronium $ )/-#+
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Vd eual or higher than totalbody water
• Di1usion to intra!elullar ,uid .Vd eual to total body water.
– 'thanol */ $ )*(-(+ – lfentanyl #2 $ )*#-77+
• Drug that binds strongly totissues. Vd higher than total
body water. – 3entanyl" 4/0 $
– ropofol" #20 $
– Digo&in"*/# $
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5hy does Vd di1erent for ea!h drug6
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• he rate of delivery and potentialamount of drug distributed into
tissues depends on8
• 9ardia! output% Regional blood ,ow%
9apillary permeability and tissuevolume.
•5ell-perfused organs (liver, kidney,
brain initially re!eive most of thedrug•$esser perfused" delivery to muscle,
most viscera, skin, and !at is
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"istribution
• determines the transport of drugs to their site of a!tion% to othersites% andto the organs of metabolism ande&!retion.
Not uniorm8
Di1eren!e in per!usion rates#
$enetrate - !apillary endothelium.
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&olume o! "istribution (&d
• values range from about #: of body volume to as high as (00 $.
• he latter ;gure is mu!h higher than anyone<s total volume% so &d is an
arti'cial concept#
• =mportan!e - it will predi!t whether the drug will reside in te blood orin te tissue#
• )ater soluble dru*s +ill reside in te blood, and !at solubledru*s +ill reside in cell membranes, adipose tissue and oter
!at-ric areas#• Volume of Distribution also relates to whether a drug is 3ree > protein
bound
• Drugs that are !harged tend to bind to serum proteins.
• rotein bound drugs form ma!romole!ular !omple&es tat cannotcross biolo*ical membranes and remain con'ned to te
bloodstream#• $atolo*ical states may also !hange Vd.
• ?e!ause Vd mathemati!ally relates blood !on!entration to dosage it may
be employed in interpretation o! laboratory results.• @seful for providing an estimate o! dosa*e% it follows that it !an help
estimate the amount of antidote to be given.
• =ndi!ate whether there is any value in trying to enhan!e elimination as%for e&le% by dialysis.
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Volume of distribution
• pparent and hypotheti!al volume inwhi!h the drug is dispersed.
ionconcentratPlasmaDose=Vd
• Why is it relevant?
• To calculate the loading dose of a drug
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Volume of Distribution
• Vd is helpful in the !onte&t of drugmonitoring.
• redi!ts whether the pra!ti!e of drugmeasurement in blood will have any!lini!al value.
• sy!hotropi! drugs su!h as tranuilizers%antidepressants% antipsy!hoti!s% mood-altering agents%et!.% !reate their e1e!ts by binding atsites within the !entral nervous system.
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• pysician +ants to administer ananestetic a*ent at a rate o! m*.rby I& in!usion# /e elimination rate
constant is 0#1 r0
1
, and te volumeo! distribution (one compartment is10 # )at loadin* dose sould berecommended i! te dru* level to
reac 2*.m immediately3
Problem no 4
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iven, in!usion rate m*.r
elimination rate 0#1 r 1
volume o! distribution 10
6e7uired concentration 2*.m
oadin* dose &d 9ss
1000m 2*.m
000 2*
0m*
:ere +e can calculate " usin* in!usion rate and elimination rateas +ell #
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Reference books say the V d of theophylline
is 0.5 L per kg of body weight.
What is the IV loading dose to give a serumtheophylline concentration of ! mg"L ina #! kg man$
=W VC or LD = C p V d
LD = (12 mg/L) (0.5 L/kg) (62 kg) = 372 mg we usually use mcg"mL %or ug"mL&' which is the same thing as mg"L
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(ctually' theophylline for in)ection is avail*able only as (minophylline
%theophylline+ethylenediamine&' which contains,0- theophylline. In this problem' we needto give a larger weight of (minophylline toget the same weight of theophylline.
/! mg heo
0.,01 2#5 mg (mino
his gives us a loading dose
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Question
• 5hat is the loading dose reuired fordrug if8
• arget !on!entration is 0 mg>$
• Vd is 0.7# $>kg
• atients weight is 7# kg
• Answer is on the next slide
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Answer: Loading Dose of Drug A
• Dose A arget 9on!entration & VD
• Vd A 0.7# $>kg & 7# kg A #2.4# $
• arget 9on!. A 0 mg>$
• Dose A 0 mg>$ & #2.4# $ A #2# mg
• his would probably be rounded to #20 oreven #00 mg
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