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Allometric scaling of xenobiotic clearance: Uncertainty versus universality

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Abstract

Statistical analysis and Monte Carlo simulation were used to characterize uncertainty in the allometric exponent (b) of xenobiotic clearance (CL). CL values for 115 xenobiotics were from published studies in which at least 3 species were used for the purpose of interspecies comparison of pharmacokinetics. The b value for each xenobiotic was calculated along with its confidence interval (CI). For 24 xenobiotics (21%), there was no correlation between log CL and log body weight. For the other 91 cases, the mean±standard deviation of the b values was 0.74±0.16; range: 0.29 to 1.2. Most (81%) of these individual b values did not differ from either 0.67 or 0.75 at P=0.05. When CL values for the subset of 91 substances were normalized to a common body weight coefficient (a), the b value for the 460 adjusted CL values was 0.74; the 99% CI was 0.71 to 0.76, which excluded 0.67. Monte Carlo simulation indicated that the wide range of observed b values could have resulted from random variability in CL values determined in a limited number of species, even though the underlying b value was 0.75. From the normalized CL values, 4 xenobiotic subgroups were examined: those that were (i) protein, and those that were (ii) eliminated mainly by renal excretion, (iii) by metabolism, or (iv) by renal excretion and metabolism combined. All subgroups except (ii) showed a b value not different from 0.75. The b value for the renal excretion subgroup (21 xenobiotics, 105 CL values) was 0.65, which differed from 0.75 but not from 0.67.

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References

  1. Schmidt-Nielsen K. Scaling: Why Is Animal Size So Important? Princeton, NJ: Cambridge University Press, 1983.

    Google Scholar 

  2. Calder WA III. Size, Function and Life History. Cambridge, MA: Harvard University Press, 1984.

    Google Scholar 

  3. West GB, Brown JH, Enquist BJ. A general model for the origin of allometric scaling laws in biology. Science. 1997;276:122–126.

    CAS  PubMed  Google Scholar 

  4. West GB, Brown JH, Enquist BJ. The fourth dimension of life: Fractal geometry and allometric scaling of organisms. Science. 1999;284:1677–1679.

    CAS  PubMed  Google Scholar 

  5. Kleiber M. Body size and metabolism. Hilgardia. 1932;6:315–353.

    CAS  Google Scholar 

  6. Heusner AA. Energy metabolism and body size. I. Is the 0.75 mass exponent of Kleiber's equation a statistical artifact? Respir Physiol. 1982;48:1–12.

    CAS  PubMed  Google Scholar 

  7. Feldman HA, McMahon TA. The 3/4 mass exponent for energy metabolism is not a statistical artifact. Respir Physiol. 1983;52:149–163.

    CAS  PubMed  Google Scholar 

  8. Banavar JR, Maritan A, Rinaldo A. Size and form in efficient transportation networks. Nature. 1999;399:130–132.

    CAS  PubMed  Google Scholar 

  9. Dodds PS, Rothman DH, Weitz JS. Re-examination of the “3/4-law” of metabolism. J Theor Biol. 2001;209:9–27.

    CAS  PubMed  Google Scholar 

  10. Boxenbaum H. Interspecies scaling, allometry, physiological time, and the ground plan of pharmacokinetics. J Pharmacokin Biopharm. 1982;10:201–227.

    CAS  Google Scholar 

  11. Sawada Y, Hanano M, Sugiyama Y, Iga T. Prediction of disposition of beta-lactam antibiotics in humans from pharmacokinetic parameters in manimals. J Pharmacokin Biopharm 1984;12:241–261.

    CAS  Google Scholar 

  12. Mordenti J. Man versus beast: Pharmacokinetic scaling in mammals. J Pharm Sci. 1986;75:1028–1040.

    CAS  PubMed  Google Scholar 

  13. Mahmood I, Balian JD. Interspecies scaling: Prediction clearance of drugs in humans. Three different approaches. Xenobiotica. 1996;26:887–895.

    CAS  PubMed  Google Scholar 

  14. Feng MR, Lou X, Brown RR, Hutchaleelaha A. Allometric pharmacokinetic scaling: Towards the prediction of human oral pharmacokinetics. Pharm Res. 2000;17:410–418.

    CAS  PubMed  Google Scholar 

  15. Mahmood I. Interspecies scaling of renally secreted drugs. Life Sci. 1998;63:2365–2371.

    CAS  PubMed  Google Scholar 

  16. McGovren SP, Williams MG, Stewart JC. Interspecies comparison of acivicin pharmacokinetics. Drug Metab Dispo. 1988;16:18–22.

    CAS  Google Scholar 

  17. Brazzell RK, Park YH, Wooldridge CB, et al. Interspecies comparison of the pharmacokinetics of aldose reductase inhibitors. Drug Metab Dispos. 1990;18:435–440.

    CAS  PubMed  Google Scholar 

  18. Bjorkman S, Redke F. Clearance of fentanyl, alfentanil, methohexitone, thiopentone and ketamine in relation to estimated hepatic blood flow in several animal species: Application to prediction of clearance in man. J Pharm Pharmacol. 2000;52:1065–1074.

    CAS  PubMed  Google Scholar 

  19. Cherkofsky SC. 1-Aminocyclopropanecarboxylic acid: Mouse to man interspecies pharmacokinetic comparisons and allometric relationships. J Pharm Sci. 1995;84:1231–1235.

    CAS  PubMed  Google Scholar 

  20. Robbie G, Chiou WL. Elucidation of human amphotericin B pharmacokinetics: Identification of a new potential factor affecting interspecies pharmacokinetic scaling. Pharm Res. 1998;15:1630–1636.

    CAS  PubMed  Google Scholar 

  21. Paxton JW, Kim SN, Whitfield LR. Pharmacokinetic and toxicity scaling of the antitumor agents amsacrine and CI-921, a new analogue, in mice, rats, rabbits, dogs, and humans. Cancer Res. 1990;50:2692–2697.

    CAS  PubMed  Google Scholar 

  22. GreneLerouge NAM, Bazin-Redureau MI, Debray M, Schermann JM. Interspecies scaling of clearance and volume of distribution for digoxin-specific Fab. Toxicol Appl Pharmacol. 1996;138:84–89.

    CAS  Google Scholar 

  23. Lave T, Dupin S, Schmidt C, Chou RC, Jaeck D, Coassolo PH. Integration of in vitro data into allometric scaling to predict hepatic metabolic clearance in man: Application to 10 extensively metabolized drugs. J Pharm Sci. 1997;86:584–590.

    CAS  PubMed  Google Scholar 

  24. Bazin-Redureau M, Pepin S, Hong G, Debray M, Scherrmann JM. Interspecies scaling of clearance and volume of distribution for horse antivenom F(ab′)2. Toxicol Appl Pharmacol. 1998;150:295–300.

    CAS  PubMed  Google Scholar 

  25. Lashev LD, Pashov DA, Marinkov TN. Interspecies differences in the pharmacokinetics of kanamycin and apramycin. Vet Res Comm. 1992;16:293–300.

    CAS  Google Scholar 

  26. Patel BA, Boudinot FD, Schinazi RF, Gallo JM, Chu CK. Comparative pharmacokinetics and interspecies scaling of 3′-azido-3′-deoxy-thymidine (AZT) in several mammalian species. J Pharmacobio-Dyn. 1990;13:206–211.

    CAS  PubMed  Google Scholar 

  27. Kurihara A, Naganuma H, Hisaoka M, Tokiwa H, Kawahara Y. Prediction of human pharmacokinetics of panipenem-betamipron, a new carbapenem, from animal data. Antimicrob Ag Chemother. 1992;36:1810–1816.

    CAS  Google Scholar 

  28. Mehta SC, Lu DR. Interspecies pharmacokinetic scaling of BSH in mice, rats, rabbits, and humans. Biopharm Drug Dispos. 1995;16:735–744.

    CAS  PubMed  Google Scholar 

  29. Bonati M, Latini R, Tognoni G. Interspecies comparison of in vivo caffeine pharmacokinetics in man, monkey, rabbit, rat, and mouse. Drug Metab Rev. 1984-85;15:1355–1383.

    CAS  PubMed  Google Scholar 

  30. Kaye B, Brearley CJ, Cussans NJ, Herron M, Humphrey MJ, Mollatt AR. Formation and pharmacokinetics of the active drug candoxatrilat in mouse, rat, rabbit, dog and man following administration of the produg candoxatril. Xenobiotica. 1997;27:1091–1102.

    CAS  PubMed  Google Scholar 

  31. Mordenti J, Chen SA, Moore JA, Ferraiolo BL, Green JD. Interspecies scaling of clearance and volume of distribution data for five therapeutic proteins. Pharm Res. 1991;8:1351–1359.

    CAS  PubMed  Google Scholar 

  32. Sawada Y, Hanano M, Sugiyama Y, Iga T. Prediction of the disposition of β-lactam antibiotics in humans from pharmacokinetic parameters in animals. J Pharmacokinet Biopharm. 1984;12:241–261.

    CAS  PubMed  Google Scholar 

  33. Matsushita H, Suzuki H, Sugiyama Y, et al. Prediction of the pharmacokinetics of cefodizime and cefotetan in humans from pharmacokinetic parameters in animals. J Pharmacobio-Dyn. 1990;13:602–611.

    CAS  PubMed  Google Scholar 

  34. Mordenti J. Pharmacokinetic scale-up: Accurate prediction of human pharmacokinetic profiles from animal data. J Pharm Sci. 1985;74:1097–1099.

    CAS  PubMed  Google Scholar 

  35. Feng MR, Loo J, Wright J. Disposition of the antipsychotic agent CI-1007 in rats, monkeys, dogs, and human cytochrome p450 2D6 extensive metabolizers: Species comparison and allometric scaling. Drug Metab Dispos. 1998;26:982–988.

    CAS  PubMed  Google Scholar 

  36. Hildebrand M. Inter-species extrapolation of pharmacokinetic data of three prostacyclin-mimetics. Prostaglandins. 1994;48:297–312.

    CAS  PubMed  Google Scholar 

  37. Ericsson H, Tholander B, Bjorkman JA, Nordlander M, Regardh CG. Pharmacokinetics of new calcium channel antagonist clevidipine in the rat, rabbit, and dog and pharmacokinetic/pharmacodynamic relationship in anesthetized dogs. Drug Metab Dispo. 1999;27:558–564.

    CAS  Google Scholar 

  38. Sangalli L, Bortolotti A, Jiritano L, Bonati M. Cyclosporine pharmacokinetics in rats and interspecies comparison in dogs, rabbits, rats, and humans. Drug Metab Dispo. 1998;16:749–753.

    Google Scholar 

  39. Kim SH, Kim WB, Lee MG. Interspecies pharmacokinetic scaling of a new carbapenem, DA-1131, in mice, rats, rabbits and dogs, and prediction of human pharmacokinetics. Biopharm Drug Dispos. 1998;19:231–235.

    CAS  PubMed  Google Scholar 

  40. Klotz U, Antonin K-H, Bieck PR. Pharmacokinetics and plasma binding of diazepam in man, dog, rabbit, guinea pig and rat. J Pharmacol Exp Ther. 1976;199:67–73.

    CAS  PubMed  Google Scholar 

  41. Kaul S, Daudekar KA, Schilling BE, Barbhaiya RH. Toxicokinetics of 2′,3′-deoxythymidine, stavudine (D4T). Drug Metab Dispos. 1999;27:1–12.

    CAS  PubMed  Google Scholar 

  42. Sanwald-Ducray P, Dow J. Prediction of the pharmacokinetic parameters of reduced-dolasetron in man using in vitro-in vivo and interspecies allometric scaling. Xenobiotica. 1997;27:189–201.

    CAS  PubMed  Google Scholar 

  43. Kawakami J, Yamamoto K, Sawada Y, Iga T. Prediction of brain delivery of ofloxacin, a new quinolone, in the human from animal data. J Pharmacokinet Biopharm. 1994;22:207–227.

    CAS  PubMed  Google Scholar 

  44. Tsunekawa Y, Hasegawa T, Nadai M, Takagi K, Nabeshima T. Interspecies differences and scaling for the pharmacokinetics of xanthine derivatives. J Pharm Pharmacol. 1992;44:594–599.

    CAS  PubMed  Google Scholar 

  45. Bregante MA, Saez P, Aramayona JJ, et al. Comparative pharmacokinetics of enrofloxacin in mice, rats, rabbits, sheep, and cows. Am J Vet Res. 1999;60:1111–1116.

    CAS  PubMed  Google Scholar 

  46. Duthu GS. Interspecies correlation of the pharmacokinetics of erythromycin, oleandomycin, and tylosin. J Pharm Sci. 1995;74:943–946.

    Google Scholar 

  47. Efthymiopoulos C, Battaglia R, Strolin Benedetti M. Animal pharmacokinetics and interspecies scaling of FCE 22101, a penem antibiotic. J Antimicrob Chemother. 1991;27:517–526.

    CAS  PubMed  Google Scholar 

  48. Jezequel SG. Fluconazole: Interspecies scaling and allometric relationships of pharmacokinetic properties. J Pharm Pharmacol. 1994;46:196–199.

    CAS  PubMed  Google Scholar 

  49. Segre G, Bianchi E, Zanolo G. Pharmacokinetics of flunoxaprofen in rats, dogs, and monkeys. J Pharm Sci. 1988;77:670–673.

    CAS  PubMed  Google Scholar 

  50. Khor SP, Amyx H, Davis ST, Nelson D, Baccanari DP, Spector T. Dihydropyrimidine dehydrogenase inactivation and 5-fluorouracil pharmacokinetics: Allometric scaling of animal data, pharmacokinetics and toxicodynamics of 5-fluorouracil in humans. Cancer Chemother Pharmacol. 1997;39:233–238.

    CAS  PubMed  Google Scholar 

  51. Clark B, Smith DA. Metabolism and excretion of a chromone carboxylic acid (FPL 52757) in various animal species. Xenobiotica. 1982;12:147–153.

    CAS  PubMed  Google Scholar 

  52. Nakajima Y, Hattori K, Shinsei M, et al. Physiologically-based pharmacokinetic analysis of grepafloxacin. Biol Pharm Bull. 2000;23:1077–1083.

    CAS  PubMed  Google Scholar 

  53. Baggot JD. Application of interspecies scaling to the bispyridinium oxime HI-6. Am J Vet Res. 1994;55:689–691.

    CAS  PubMed  Google Scholar 

  54. Lave T, Levet-Trafit B, Schmitt-Hoffmann AH, et al. Interspecies scaling of interferon disposition and comparison of allometric scaling with concentration-time transformations. J Pharm Sci. 1995;84:1285–1290.

    CAS  PubMed  Google Scholar 

  55. Sakai T, Hamada T, Awata N, Watanabe J. Pharmacokinetics of an antiallergic agent, 1-(2-ethoxyethyl)-2-(hexahydro-4-methyl-1H-1,4-diazepin-1-yl)-1H-benzimidazole difumarate (KG-2413) after oral administration: Interspecies differences in rats, guinea pigs and dogs. J Pharmacobio-Dyn. 1989;12:530–536.

    CAS  PubMed  Google Scholar 

  56. Lave T, Saner A, Coassolo P, Brandt R, Schmitt-Hoffman AH, Chou RC. Animal pharmacokinetics and interspecies scaling from animals to man of lamifiban, a new platelet aggregation inhibitor. J Pharm Pharmacol. 1996;48:573–577.

    CAS  PubMed  Google Scholar 

  57. Richter WF, Gallati H, Schiller CD. Animal pharmacokinetics of the tumor necrosis factor receptor-immunoglobulin fusion protein lenercept and their extrapolation to humans. Drug Metab Dispos. 1999;27:21–25.

    CAS  PubMed  Google Scholar 

  58. Lapka R, Rejholec V, Sechser T, Peterkova M, Smid M. Interspecies pharmacokinetic scaling of metazosin, a novel alpha-adrenergic antagonist. Biopharm Drug Dispo. 1989;10:581–589.

    CAS  Google Scholar 

  59. Ahr H-J, Boberg M, Brendel E, Krause HP, Steinke W. Pharmacokinetics of miglitol: Absorption, distribution, metabolism, and excretion following administration to rats, dogs, and man. Arzneim Forsch. 1997;47:734–745.

    CAS  Google Scholar 

  60. Siefert HM, Domdey-Bette A, Henninger K, Hucke F, Kohlsdorfer C, Stass HH. Pharmacokinetics of the 8-methoxyquinolone, moxifloxacin: A comparison in humans and other mammalian species. J Antimicrob Chemother. 1999;43(Suppl. B):69–76.

    CAS  PubMed  Google Scholar 

  61. Lave T, Portmann R, Schenker G, et al. Interspecies pharmacokinetic comparisons and allometric scaling of napsagatran, a low molecular weigrobin inhibitor. J Pharm Pharmacol. 1999;51:85–91.

    CAS  PubMed  Google Scholar 

  62. Higuchi S, Shiobara Y. Comparative pharmacokinetics of nicardipine hydrochloride, a new vasodilator, in various species. Xenobiotica. 1980;10:447–454.

    CAS  PubMed  Google Scholar 

  63. Mitsuhashi Y, Sugiyama Y, Ozawa S, et al. Prediction of ACNU plasma concentration-time profiles in humans by animal scale-up. Cancer Chemother Pharmacol. 1990;27:20–26.

    CAS  PubMed  Google Scholar 

  64. Yoshimura M, Kojima J, Ito T, Suzuki J. Pharmacokinetics of nipradilol (K-351), a new antihypertensive agent. I. Studies on interspecies variation in laboratory animals. J Pharmacobio-Dyn. 1985;8:738–750.

    CAS  PubMed  Google Scholar 

  65. Gombar CT, Harrington GW, Polypiw HM Jr, et al. Interspecies scaling of the pharmacokinetics of Nnitrosodimethylamine. Cancer Res. 1990;50:4366–4370.

    CAS  PubMed  Google Scholar 

  66. Mukai H, Watanabe S, Tsuchida K, Morino A. Pharmacokinetics of NS-49, a phenethylamine class α1A-adrenoceptor agonist, at therapeutic doses in several animal species and interspecies scaling of its pharmacokinetic parameters. Int J Pharm. 1999;186:215–222.

    CAS  PubMed  Google Scholar 

  67. Owens SM, Hardwick WC, Blackall D. Phencyclidine pharmacokinetic scaling among species. J Pharmacol Exp Ther. 1987;242:96–101.

    CAS  PubMed  Google Scholar 

  68. Ishigami M, Saburomaru K, Niino K, et al. Pharmacokinetics of procaterol in the rat, rabbit, and beagle dog. Arzneim Forsch. 1979;29:266–270.

    CAS  Google Scholar 

  69. Khor AP, McCarthy K, DuPont M, Murray K, Timony G. Pharmacokinetics, pharmacodynamics, allometry, and dose selection of rPSGL-Ig for phase I trial. J Pharmacol Exp Ther. 2000;293:618–624.

    CAS  PubMed  Google Scholar 

  70. Mordenti J, Osaka G, Garcia K, Thomsen K, Licko V, Meng G. Pharmacokinetics and interspecies scaling of recombinant human factor VIII. Toxicol Appl Pharmacol. 1996;136:75–78.

    CAS  PubMed  Google Scholar 

  71. Coassolo P, Fischli W, Clozel J-P, Chou RC. Pharmacokinetics of remikiren, a potent orally active inhibitor of human renin, in rat, dog, and primates. Xenobiotica. 1996;26:333–345.

    CAS  PubMed  Google Scholar 

  72. Widman M, Nilsson LB, Bryske B, Lundstrom J. Disposition of remoxipride in different species. Arzneim Forsch. 1993;43:287–297.

    CAS  Google Scholar 

  73. Lashev L, Pashov D, Kanelov I. Species specific pharmacokinetics of rolitetracycline. J Vet Med A. 1995;42:201–208.

    CAS  Google Scholar 

  74. Herault JP, Donat F, Barzu T, et al. Pharmacokinetic study of three synthetic AT-binding pentasaccharides in various animal species-extrapolation to humans. Blood Coagul Fibrinol. 1997;8:161–167.

    CAS  Google Scholar 

  75. Ward KW, Azzarano LM, Bondinell WE, et al. Preclinical pharmacokinetics and interspecies scaling of a novel vitronectin receptor antagonist. Drug Metab Dispos. 1999;27:1232–1241.

    CAS  PubMed  Google Scholar 

  76. Lin C, Gupta S, Loebenberg D, Cayen MN. Pharmacokinetics of an everninomicin (SCH 27899) in mice, rats, rabbits, and cynomolgus monkeys following intravenous administration. Antimicrob Ag Chemother. 2000;44:916–919.

    CAS  Google Scholar 

  77. Chung M, Radwanski E, Loebenberg D, et al. Interspecies pharmacokinetic scaling of Sch 34343. J Antimicrob Chemother. 1985;15(Suppl. C):227–233.

    PubMed  Google Scholar 

  78. Hinderling PH, Dilea C, Koziol T, Millington G. Comparative kinetics of sematilide in four species. Drug Metab Dispo. 1993;21:662–669.

    CAS  Google Scholar 

  79. Walker DK, Ackland MJ, James GC, et al. Pharmacokinetics and metabolism of sildenafil in mouse, rat, rabbit, dog, and man. Xenobiotica. 1999;29:297–310.

    CAS  PubMed  Google Scholar 

  80. Brocks DR, Freed MI, Martin DE, et al. Interspecies pharmacokinetics of a novel hematoregulatory peptide (SK&F 107647) in rats, dogs, and oncologic patients. Pharm Res. 1996;13:794–797.

    CAS  PubMed  Google Scholar 

  81. Cosson VF, Fuseau E, Efthymiopoulos C, Bye A. Mixed effect modeling of sumatriptan pharmacokinetics during drug development. I: Interspecies allometric scaling. J Pharmacokin Biopharm. 1997;25:149–167.

    CAS  Google Scholar 

  82. Leusch A, Troger W, Greischel A, Roth W. Pharmacokinetics of the M1-agonist talsaclidine in mouse, rat, rabbit, and monkey, and extrapolation to man. Xenobiotica. 2000;30:797–813.

    CAS  PubMed  Google Scholar 

  83. van Hoogdalem EJ, Soeishi Y, Matsushima H, Higuchi S. Disposition of the selective α1A-adrenoceptor antagonist tamsulosin in humans: Comparison with data from interspecies scaling. J Pharm Sci. 1997;86:1156–1161.

    PubMed  Google Scholar 

  84. Cruze CA, Kelm GR, Meredith MP. Interspecies scaling of tebufelone pharmacokinetic data and application to preclinical toxicology. Pharm Res. 1995;12:895–901.

    CAS  PubMed  Google Scholar 

  85. Gaspari F, Bonati M. Interspecies metabolism and pharmacokinetic scaling of theophylline disposition. Drug Metab Rev. 1990;22:179–207.

    CAS  PubMed  Google Scholar 

  86. Davi H, Tronquet C, Calx J, et al. Disposition of tiludronate (Skelid) in animals. Xenobiotica. 1999;29:1017–1031.

    CAS  PubMed  Google Scholar 

  87. Pahlman I, Kankaanranta S, Palmer L. Pharmacokinetics of tolterodine, a muscarinic receptor antagonist, in mouse, rat and dog. Arzneim Forsch. 2001;51:134–144.

    CAS  Google Scholar 

  88. Tanaka E, Ishikawa A, Horie T. In vivo and in vitro trimethadione oxidation activity of the liver from various animal species including mouse, hamster, rat, rabbit, dog, monkey and human. Human Exp Toxicol. 1999;18:12–16.

    CAS  Google Scholar 

  89. Izumi T, Enomoto S, Hosiyama K, et al. Prediction of the human pharmacokinetics of troglitazone, a new and extensively metabolized antidiabetic agent, after oral administration, with an animal scale-up approach. J Pharmacol Exp Ther. 1996;277:1630–1641.

    CAS  PubMed  Google Scholar 

  90. Grindel JM, O'Neil PG, Yorgey KA, et al. The metabolism of zomepirac sodium I. Disposition in laboratory animals and man. Drug Metab Dispo. 1980;8:343–348.

    CAS  Google Scholar 

  91. Singer MA, Morton AR. Mouse to elephant: Biological scaling and Kt/V. Am J Kidney Dis. 2000;35:306–309.

    CAS  PubMed  Google Scholar 

  92. Singer MA. Of mice and men and elephants: Metabolic rate sets glomerular filtration rate. Am J Kidney Dis. 2001;37:164–178.

    CAS  PubMed  Google Scholar 

  93. Edwards NA. Scaling of renal functions in mammals. Comp Biochem Physiol. 1975;52A:63–66.

    Google Scholar 

  94. Hayton WL. Maturation and growth of renal function: Dosing renally cleared drugs in children. AAPS PharmSci. 2000;2(1), article 3.

    Google Scholar 

  95. Adolph EF. Quantitative relations in the physiological constituents of mammals. Science. 1949;109:579–585.

    CAS  PubMed  Google Scholar 

  96. Rubner M. Über den einfluss der körpergrösse auf stoff und kraftwechsel. Z Biol. 1883;19:535–562.

    Google Scholar 

  97. Heusner A. Energy metabolism and body size. II. Dimensional analysis and energetic non-similarity. Resp Physiol. 1982;48:13–25.

    CAS  Google Scholar 

  98. West GB. The origin of universal scaling laws in biology. Physica A. 1999;263:104–113.

    Google Scholar 

  99. Murray CD. The physiological principle of minimum work. I. The vascular system and the cost of blood volume. Proc Natl Acad Sci U S A. 1926;12:207–214.

    CAS  PubMed Central  PubMed  Google Scholar 

  100. Cohn DL. Optimal systems: I. The vascular system. Bull Math Biophys. 1954;16:59–74.

    Google Scholar 

  101. Cohn DL. Optimal systems: II. The vascular system. Bull Math Biophys. 1955;17:219–227.

    Google Scholar 

  102. Bonate PL, Howard D. Prospective allometic scaling: Does the emperor have clothes? J Clin Pharmacol. 2000;40:665–670.

    CAS  PubMed  Google Scholar 

  103. Mahmood I. Critique of prospective allometric scaling: Does the emperor have clothes? J Clin Pharmacol. 2000;40:671–674.

    Google Scholar 

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  1. Division of Pharmaceutics, College of Pharmacy, The Ohio State University, 500 W. 12th Ave, 43210-1291, Columbus, OH

    Teh-Min Hu & William L. Hayton

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Published: November 21, 2001

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Hu, TM., Hayton, W.L. Allometric scaling of xenobiotic clearance: Uncertainty versus universality. AAPS PharmSci 3, 29 (2001). https://doi.org/10.1208/ps030429

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