# PharmPK Discussion - Blood volume formula

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• On 8 Jan 2001 at 16:50:02, "GSCC-Nuclear Medicine Clinic" (nuclmed.gscancer.aaa.worldnet.att.net) sent the message
`Hi everyone,Can anyone give me the formula to calculate blood volume based on weightand hematocrit for man?  I would also like a reference for this formulaif possible.Dion YeldellGarden State Cancer Center520 Belleville AveBelleville, New Jersey 07109 USA973-844-7111Fax 973-844-7120dionyeldell.gscancer.-a-.worldnet.att.net`
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• On 10 Jan 2001 at 10:55:11, "Ronald Kavanagh 301-827-4254 FAX 301-827-4264" (KAVANAGHR.aaa.cder.fda.gov) sent the message
`Following is an example of calculating approximate fluid volumes in ahuman by using the rule of 2/3's.I don't have and original citation.	Fluid Volumes	Using Rule of 2/3's & 70 kg person	2/3 = 	0.666666667	Total Body Weight 	TBWt	70.0 kg	Hcrit = 0.4							L.	L/kgTotal Body Water		TBW	(2/3*TBWt)	46.7	0.67Intracellular Fluid Volume	ICF	(2/3*TBWater)	31.1	0.44Extracellular Fluid Volume	ECF	(1/3*TBWater)	15.6	0.222Extravascular Fluid Vol 	EVF	(2/3 * ECF)	10.4	0.148aka Interstitual Fluid		(ISF)Intravascular Fluid Vol 	IVF	(1/3 * ECF)	5.2	0.074Blood Volume)Plasma volume			PV	(IVF*(1-Hcrit))	3.1	0.0444Cell Volume			CV	(IVF*Hcrit)	2.1	0.0300******Ronald E. Kavanagh. B.S. Pharm., Pharm.D., Ph.D.Food & Drug AdministrationOffice of Clinical Pharmacology and Biopharmaceutics5600 Fishers Lane	HFD-870Rockville, MD  20857Phone:	301-827-4254	FAX:	301-827-4264Office:	Parklawn (PKLN) 17B-30	e-mail:	kavanaghr.at.cder.fda.gov******`
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• On 12 Jan 2001 at 13:30:40, "He, Yan-Ling" (YHE.-a-.PARTNERS.ORG) sent the message
`The following message was posted to: PharmPKI and my colleagues in Osaka University, Japan, had measured theblood volume inpatients with ICG.   The results were published in "Crit. Care Med.26:1446-1451, 1998, entitled :"Measurement of blood volume using indocyaninegreen measured with pulse-spectrophotometry: The reproductivity andreliability". We also published another paper demonstrating the blood volumechange in parturients in Anesthesiology (91:1571-1576, 1999). I wishthis helps.Yan-Ling He, B.Sc., M.Sc., Ph.D., D. Phil.-----Department of Anesthesia and Critical CareMassachusetts General HospitalHarvard Medical School55 Fruit St. BostonMA 02114-2696USAE-mail: Yhe.at.partners.org ----`
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• On 13 Jan 2001 at 14:32:51, ml11439.-at-.goodnet.com sent the message
`The following message was posted to: PharmPKDion,     A formula for calculating blood volume is available in Guyton&Hall's Textbook of Medical Physiology. The formula first requiresthe determination of plasma volume using the "indicator-dilutionprinciple". The indicator could be Evan's blue dye or albumin labeledwith radioactive iodine (I125-albumin). The concentration of theindicator is measured in the plasma, and by the conservation ofmass the plasma volume is equal to:       Volume of plasma=  (vol injected)x(Concentration injected)/                           (plasma concentration measured)      Determination of hematocrit (fraction of blood volume composedof cells) will allow the calculation of blood volume using the plasmavolume calculated above:     Total blood volume=  Plasma volume/(1-hematocrit)     Another method of measuring blood volume is to inject red bloodcells labeled with radioactive chromium, and apply the indicator-dilutionprinciple after determining the concentration of radioactively labeledred blood cells in the circulation.                                       Mike Leibold, PharmD, RPh                                       ML11439.at.goodnet.com`
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• On 13 Jan 2001 at 15:29:56, Nick Holford (n.holford.at.auckland.ac.nz) sent the message
`The following message was posted to: PharmPKMike Leibold wrote:>       A formula for calculating blood volume is available in Guyton&>  Hall's Textbook of Medical Physiology. The formula first requires>  the determination of plasma volume using the "indicator-dilution>  principle". The indicator could be Evan's blue dye or albumin labeled>  with radioactive iodine (I125-albumin). The concentration of the>  indicator is measured in the plasma, and by the conservation of>  mass the plasma volume is equal to:>>         Volume of plasma=  (vol injected)x(Concentration injected)/>                             (plasma concentration measured)This is an example of why physiologists need to learn somethingpractical about pharmacokinetics. The formula shown above makes theuntenable assumptions that either albumin or Evan's Blue never leavethe plasma compartment which implies also that they are neithereliminated nor distributed elsewhere. Application of apharmacokinetic model to the time course of concentrations would bemuch more sensible to estimate the central volume of distributionrather than relying on a single concentration and two unreasonableassumptions.Nick--Nick Holford, Divn Pharmacology & Clinical PharmacologyUniversity of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealandemail:n.holford.-a-.auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.htm`
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• On 14 Jan 2001 at 18:41:18, uceph hijazi (uceph_hijazi.-at-.yahoo.fr) sent the message
`The following message was posted to: PharmPKTo Dr. Nick Halford and to Dr.Mike Leibold,I prefer the physiological method for thedetermination of the volume of central compartement(plasma volume), because neither evan's blue norlabelled albumin are distributed out side the plasma.Their plasma concentrations will be constant over along period of time to permitt an accurate measurementof the plasma volume.any error in this method would benegligible.Mean while the use of a PK model to get the volume ofcentral compartment, from a PK profile is subjected tomore error, since we introduced other variables suchas the variations in renal and hepatic functions thatare responsible for the decline in the concentrationtime profile.=3D=3D=3D=3D=3DYoussef HijaziH=F4pital neurologique et neurochirurgicaleUNITE DE PHARMACOLOGIE CLINIQUEd=E9partement de dosage de m=E9dicaments et de Pharmacocin=E9tiqueDirecteur: Professeur Roselyne BoulieuB.P. Lyon Montchat 69394 Lyon Cedex 03-FRANCETel: 04 72 35 72 45`
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• On 15 Jan 2001 at 10:36:06, Nick Holford (n.holford.aaa.auckland.ac.nz) sent the message
`The following message was posted to: PharmPK"uceph hijazi (by way of David_Bourne)" wrote:>>  To Dr. Nick Halford and to Dr.Mike Leibold,(Please note my name is Holford)>  I prefer the physiological method for the>  determination of the volume of central compartement>  (plasma volume), because neither evan's blue nor>  labelled albumin are distributed out side the plasma.If albumin does not distribute out of plasma then I assume that meansalbumin cannot get into plasma e.g. from the liver. So how do youexplain the existence of endogenous albumin in plasma?>  Their plasma concentrations will be constant over a>  long period of time to permitt an accurate measurement>  of the plasma volume.any error in this method would be>  negligible.Do you have any data to support your speculation? What is a longperiod of time?>  Mean while the use of a PK model to get the volume of>  central compartment, from a PK profile is subjected to>  more error, since we introduced other variables such>  as the variations in renal and hepatic functions that>  are responsible for the decline in the concentration>  time profile.I don't think you know what a PK model means. There is no need toinclude renal or hepatic function in the description of plasmaconcentrations.--Nick Holford, Divn Pharmacology & Clinical PharmacologyUniversity of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealandemail:n.holford.aaa.auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.htm`
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• On 16 Jan 2001 at 10:26:16, "He, Yan-Ling" (YHE.-at-.PARTNERS.ORG) sent the message
`The following message was posted to: PharmPKI completely agree with Nick, not only because it is theoretically sensible butalso we have proved that estimating blood volume based on a singleconcentrationcould cause a more than 30% error.  This is especially problematicwhen treatingpatients in critical care unit.  Measuring blood volume of patients with eitherEvans Blue or radiolabelled albumin is quite invasive in terms ofblood samplingand dye or radioactivity pollution.  The recently developed methodology ofmeasuring ICG blood concentration with pulse-sepctrophotometry can be achievedby applying a probe on patients' finger or ear and no blood sampling isnecessary.  The blood concentration of ICG can be monitored at every pulseinterval, therefore, precise pharmacokinetic model can be applied.Please referto: Crit Care Med. 26:1446-1451, 1998Yan-Ling HE, Ph.D., D.Phil.`
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• On 17 May 2001 at 23:03:31, "Shailesh Vyas" (svyas.-at-.columbus.rr.com) sent the message
`Does the rule of 2/3rd as described by Dr.Ronald Kavanagh work in the =same manner for both male and female or is there a conversion =factor(like one you see in creatinine clearance,CrCl female=3D0.85xCrCl =male)?Thanks.Shailesh Vyas`
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• On 24 May 2001 at 16:27:04, "Ronald Kavanagh 301-827-4254 FAX 301-827-4264" (KAVANAGHR.at.cder.fda.gov) sent the message
`The rule of 2/3rds is simply a rough rule of thumb. I learned it in manyyears ago and don't have a reference or any additional information.I don't know if it's +/- 10%, 15% or whatever.I use it for both males and females as it's based on total body weight.For those who don't remember, the rule of 2/3rds is a rough rule ofthumb to estimate various fluid volumes in humans.Total Body Water (TBW) = 2/3 * Total Body Weight (TBWt)Intracellular Fluid Volume (ICF) = 2/3 * Total Body Water[Extracellular Fluid Volume (ECF) = TBW - ICF]Interstitial Fluid Volume (IFV) = 2/3 * ECFBlood Volume (BV) = ECF - IFVPlasma Volume = 2/3 * BVEx.70 kg * 2/3 = 46.7 L (TBW)46.7 L * 2/3 = 31.1 L (ICF)46.7 (TBW) - 31.1 (ICF) = 15.6 L (ECF)15.6 * 2/3 = 10.4 L (IFV)15.6 - 10.4 = 5.2 L (Blood Volume)For estimating plasma and red blood cell volume, instead of using 2/3'swe use an average for hematocrit of 40%5.2 * 0.6 = 3.1 L (Plasma Volume)Another rough rule of thumb is that blood volume is ~5 L and plasmavolume is ~3 L. So they're close.Obviously hematocrit varies around 40% and is slightly lower for women.i.e. 38-47% for F 40-54% for M.In addition to variations in hematocrit there may be variations based onhydration, status, body composition, etc..  Consequently, the rule of2/3's is only a rough approximation.Ronald E. Kavanagh. B.S. Pharm., Pharm.D., Ph.D.Food & Drug AdministrationOffice of Clinical Pharmacology and BiopharmaceuticsWOC-II	Rm 4061		HFD-8601451 Rockville PikeRockville, MD  20852Phone:	301-594-6650	FAX:	301-480-3212Office:	Woodmont (WOC-II) Rm. 4061	e-mail:	kavanaghr.-a-.cder.fda.gov`
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