# PharmPK Discussion - Allometry and Dedrick Plots

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• On 16 Apr 2007 at 12:09:33, Tonika Bohnert (tonika.bohnert.aaa.biogenidec.com) sent the message
`Hello,I am new to the field of allometry and am having some troubles withone particular prediction that I am working on. For this onecompound, we have IV CL(mL/min) and Vss(L/kg) respectively asfollows: Mouse (0.0555, 0.778), Rat (0.65, 0.548), Dog (20.28, 1.1).When I plot log Cl vs log BW, I get very nice straight lines for bothCl and Vss with equations being : log CL = 0.9488 log BW + 0.3106 andlog Vss = 1.069 log BW - 0.837 with R-squared values of 0.999 forboth CL and Vss. However, after this for concentration projections,when I convert the concentrations and times to plot Complex Dedrickplots (I am using Complex Dedrick since exponent of Vss is greaterthan 1) , instead of overlapping plots , I get almost 3 parallelplots with C0 for Dog about 10-fold higher than rat and C0-rat being10 fold higher than C0-mouse (on a log scale). When the plots areoverlapping, then concentration vs time projections calculations arestraight forward but when the plots are parallel with about 10-folddifference in their C0 values , then how does one proceed to do theseprojections? Does this mean allometry fails to predict conc vs time(for a specified dose & BW of another species in question/prediction). Do we need to get data from another species to make anyfurther predictions?For Dedrick plots I am plotting C/(Dose/BW d) vs Time/ BW  d-b whered = 1.069 and b = 0.9488 from above equations.For another compound in the same series we got v.similar data but forthat we also had monkey data and surprisingly, the monkey and ratplots were exactly superimposible and the dog had 10-fold higher C0(but parallel plot) and mouse had 10-fold lower C0 (again parallelplot). So what does this tell us?Thanks so much for any advice/input on this. Shall be eagerly lookingforward to it !Tonika Bohnert, Ph.DDMPK.Biogen Idec Inc.,15 Cambridge CenterCambridge, MA 02142`
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• On 17 Apr 2007 at 08:57:44, Nick Holford (n.holford.-a-.auckland.ac.nz) sent the message
`The following message was posted to: PharmPKTonika,It is essentially impossible with such small amounts of data toestimate allometric model exponents with any hope they might beunbiased and precise. The theoretically correct values for theexponent of Clearance of 0.75 and for volume is 1.0.What are you trying to do with your allometric predictions?Nick--Nick Holford, Dept Pharmacology & Clinical PharmacologyUniversity of Auckland, 85 Park Rd, Private Bag 92019, Auckland, NewZealandemail:n.holford.at.auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556http://www.health.auckland.ac.nz/pharmacology/staff/nholford/`
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• On 17 Apr 2007 at 10:16:18, "Ma Guangli" (guanglima.-a-.gmail.com) sent the message
`Dear Tonika,     Although there are many allmetric methods, why not to examinethe molecular properties of your compound first? The studiedmolecular descriptors are simple.Jolivette LJ, Ward KW 2005. Extrapolation of human pharmacokineticparameters from rat, dog, and monkey data: Molecular propertiesassociated with extrapolative success or failure. J Pharm Sci  94(7):1467-1483.Evans CA, Jolivette LJ, Nagilla R, Ward KW 2006. Extrapolation ofpreclinical pharmacokinetics and molecular feature analysis of"discovery-like" molecules to predict human pharmacokinetics. DrugMetab Dispos  34(7):1255-1265.Guangli`
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