The allometric approach for interspecies scaling of pharmacokinetics and toxicity of anti-cancer drugs

Clinical and Experimental Pharmacology & Physiology
J W Paxton

Abstract

1. The rationale for extrapolation or 'scaling' across animal species is based on their underlying anatomical, physiological and biochemical similarities. 2. Research carried out in the 19th and early 20th century resulted in Benedict's famous 'mouse-to-elephant' graph which showed that the log of the basal metabolic rate plotted against the log of bodyweight (W) produced a straight line with a slope of 0.76. Since then it has become apparent that a number of other physiological variables (Y) exhibit a similar relationship which can be represented by the general allometric equation, Y = alpha W beta; where beta is the slope of the log-log plot and alpha is the intercept on the y axis. 3. The major pharmacokinetic parameters such as clearance and volume of distribution of many drugs are also related to W in a similar manner. 4. This empirical approach does not require a strong mathematical background and offers a relatively simple method of predicting the kinetics of anti-cancer drugs in patients from pre-clinical animal data. 5. The occurrence of major qualitative and quantitative differences in the metabolism of drugs between species is probably the single greatest complicating factor in the use of animals as predictors of dru...Continue Reading

References

Oct 1, 1992·Comparative Biochemistry and Physiology. C, Comparative Pharmacology and Toxicology·W A RitschelA S Hussain
Jun 1, 1992·Risk Analysis : an Official Publication of the Society for Risk Analysis·K WatanabeL Zeise
Aug 15, 1990·Journal of the National Cancer Institute·J M CollinsB A Chabner
Jan 1, 1990·Cancer Chemotherapy and Pharmacology·Y MitsuhashiT Kobayashi
Jan 1, 1990·Drug Metabolism Reviews·F Gaspari, M Bonati
Nov 1, 1990·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·R M Ings
Sep 1, 1986·Journal of Pharmaceutical Sciences·J Mordenti
Sep 1, 1986·Regulatory Toxicology and Pharmacology : RTP·I W DavidsonR P Beliles
Jan 1, 1970·Clinical Pharmacology and Therapeutics·P S ScheinD P Rall
Apr 1, 1984·European Journal of Drug Metabolism and Pharmacokinetics·H H WittekindL P Balant
Jun 1, 1984·Journal of Pharmacokinetics and Biopharmaceutics·Y SawadaT Iga
Apr 1, 1984·European Journal of Drug Metabolism and Pharmacokinetics·H Boxenbaum, J B Fertig
Apr 1, 1982·Journal of Pharmacokinetics and Biopharmaceutics·H Boxenbaum

❮ Previous
Next ❯

Citations

Mar 1, 2012·Cancer Chemotherapy and Pharmacology·Elizabeth RayburnRuiwen Zhang
Sep 12, 2012·Theoretical Biology & Medical Modelling·Ray Greek, Mark J Rice
Jun 24, 2009·Regulatory Toxicology and Pharmacology : RTP·David R JonesKeith R Abrams
Feb 27, 2007·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·Carlos Arturo NavasMarcio Martins
Jun 25, 2013·Progress in Biophysics and Molecular Biology·Ray Greek, Lawrence A Hansen
Jan 1, 2012·Personalized Medicine·Ray GreekMark J Rice
Apr 20, 2001·Journal of Medicinal Chemistry·H van De WaterbeemdD K Walker

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.