# PharmPK Discussion - Body surface area calculation

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• On 18 Oct 1996 at 13:57:23, Tom Wallace (twallace.-a-.aronex.com) sent the message
`I need to convert a human drug dose in mg/(meter squared) to a comparabledose in rats.  How does one calculate the surface area of a rat.  Is therea formula?  In addition, how can the human dose be converted into a ratdose on a mg/kg basis?`
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• On 21 Oct 1996 at 09:49:43, Prasad Tata (Prasadt.-at-.OTSUKA.OAPI.COM) sent the message
`Person to contact regaridng this issue is Dr. Harold BoxenbaumTel (301) 424-2806`
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• On 21 Oct 1996 at 09:50:31, Duncan Jodrell (jodrell.-at-.icrf.icnet.uk) sent the message
`  I do not know how to calculate the surface area of a rat! .... but Ithink you don't need to.  I have always used the conversion  1 mg/kg = 6 mg/sq.m for rats.  (In mice 1 mg/kg = 3 mg/sq.m)  Therefore you should be able to work out an appropriate dose if you knowthe mg/sq.m dose in man.  Hope this is helpful - others may disagree, it will be interesting tosee if there any other comments.  Duncan Jodrell  Edinburgh`
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• On 21 Oct 1996 at 09:50:45, Joan Korth-Bradley (KorthBJ.-a-.war.wyeth.com) sent the message
`It depends upon the rat and the person.  The questions you ask arespelled out in:Freireich EJ et al.  Quantitative comparison of toxicity of anticanceragents in mouse, rat, hamster, dog, monkey and man.  Cancer ChemoReports  1966;50:219-244.Another paper to look for is:Monro A, and Mordenti J.  Expression of exposure in negativecarcinogenticity studies:  dose/body weight, dose/body surface are orplasma concentrations?  Toxicolgy Pathology 1995;23:187-98.which has a comprehensive table describing physiological differencesbetween rats and humans to guide your allometric conversions.Joan K-B`
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• On 21 Oct 1996 at 09:51:25, Gabrielsson Johan (JOHAN.GABRIELSSON.-at-.arcus.se.astra.com) sent the message
`A good reference to start with is 'First-time-in-human dose selection:Allometric thoughts and perspectives, by Boxenbaum and Dilea,J.Clin.Pharmacol. 35:957-966(1995).`
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• On 22 Oct 1996 at 11:08:50, rajesh krishna (rkrishna.-a-.unixg.ubc.ca) sent the message
`You could use pharmacokinetic-based approach to convert human dose to ratdose using AUC or PBPK methods.  These are outlined in a review writtenby Voisin et al., entitled "Extrapolation of animal toxicity to humans:interspecies comparisons in drug development" that appeared in RegulatoryToxicology and Pharmacology. 12(2): 107-116, 1990 (October).Rajesh Krishna`
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• On 22 Oct 1996 at 11:10:01, Prasad Tata (Prasadt.at.OTSUKA.OAPI.COM) sent the message
`Species      Body Wt.(KG)    Body Surf. Area (Sq. Mtr)    Km FactorMouse          0.2              0.0066                      3.0Rat            0.15             0.025                       5.9Monkey         3.0              0.24                       12Dog            8.0              0.40                       20Human  Child       20.0              0.80                       25   Adult      60.0              1.60                       37Ref: Freireich E.J. et.al.  Cancer Chemother. Reports  1966, 50(4) 219-244.Body Surface area dependent Dose conversion Rat (150g) to Man (60 Kg) is 1/7 the rat dose Dog (8Kg) to Human (60 Kg) is 1/2 the dog dose.Hope this helps you,Prasad Tata, Ph.D.Otsuka America Pharmaceuticals Inc.`
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• On 13 Nov 1996 at 11:37:07, "Joyce Mordenti" (jm.at.gene.COM) sent the message
`Calculation of APPROXIMATE body surface area (BSA) uses simpleallometric relationship based on body weight (W):    BSA = W to the 0.67 power.The Freireich data are reanalyzed (by allometric approach) in "DosageRegimen Design for Pharmaceutical Studies Conducted in Animals," J.Mordenti, J. Pharm. Sci., 75:852-57, 1986.  A good discussion onallometry and tables of BSA data appear in "Extrapolation ofToxicological and Pharmacological Data from Animals to Humans," W.Chappell & J. Mordenti, Advances in Drug Research, Vol. 20, 1-116, 1991(published by Academic Press Ltd).    - regards, JoycePS  Joan, I was surprised by your plug for the Monro/Mordenti paper.  Ididn't expect many pharmacokineticists to discover it.  Thanks!`
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• On 14 Nov 1996 at 12:11:21, Nick Holford (n.holford.-at-.auckland.ac.nz) sent the message
`>> Calculation of APPROXIMATE body surface area (BSA) uses simple> allometric relationship based on body weight (W):>>     BSA = W to the 0.67 power.>But why use BSA in preference to more empirically sound allometricmodels?The only thing going for BSA is tradition. The usual Du Bois & Du Boismodel for BSA is based on 10 individuals. An allometric exponent of 3/4instead of 2/3 is based on a multitude of observations across severalorders of magnitude of weight and varieties of animals.See:Peters RH. The ecological implications of body size. Cambridge:Cambridge University Press, 1983This is THE reference work for a wider view of allometrics.Holford NHG A Size Standard for Pharmacokinetics Clin.Pharmacokin. 1996;30:329-332Compares common size models for clearance and shows the potentialweakness especially at low body weights e.g. children in comparison tothe 3/4 exponent model.--Nick Holford, Dept Pharmacology & Clinical PharmacologyUniversity of Auckland, Private Bag 92019, Auckland, New Zealandemail:n.holford.at.auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.html`
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