Abstract
Allometric scaling is an empirical examination of the relationships between the pharmacokinetic parameters and size (usually body weight), but it can also involve brain weight for metabolized drug. Through all species, the protein binding of sumatriptan is similar (14-16%). and its metabolic pathway undergoes extensive oxidative deamination involving the monoamine oxidase A isoenzyme. These similarities across species suggested the possible relevance of an allometric analysis. Toxicokinetic data were collected from rats, pregnant rabbits, and dogs in animal pharmacokinetic studies where sumatriptan was administered intravenously to the animals at doses of 5 mg/kg. 0.25 mg/kg, and 1 mg, kg, respectively. Animal data were pooled and analyzed in one step using a mixed effect modeling (population) approach. The kinetic parameters predicted in any species were close to the observed values by species: 77 L/hr vs. 80 L/hr in man for total clearance, 137 L vs. 119 L for distribution volume at steady state. The value of the mixed effect modeling approach compared to the two-step method was demonstrated especially with the possibility of including covariates to describe the status of animal (e.g., pregnancy) in the model. Knowledge of the animal kinetics, dynamics, and metabolism of a drug contributes to optimal and expeditious development. Valuable information for the design of the first-dose-in-man study may emerge from more creative data analysis based on all the information collected during the preclinical and ongoing nonclinical evaluation of a new drug.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
J. Mordenti. Forecasting cephalosporin and monobactam antibiotic half-lives in humans from data collected in laboratory animals. Antimicrob. Agents Chemother. 27:887–891 (1985).
J. Mordenti. Pharmacokinetic scale-up: Accurate prediction of human pharmacokinetic profiles from animal data. J. Pharm. Sci. 74:1097–1099 (1985).
J. Mordenti, S. A. Chen, J. A. Moore, B. L. Ferraiolo, and J. D. Green. Interspecies scaling of clearance and volume of distribution data for five therapeutic proteins. Pharm. Res. 8:1351–1359 (1991).
C. Efthymiopoulos, R. Battaglia, and M. Strolin Benedetti. Animal pharmacokinetics and interspecies scaling of FCE 22101, a penem antibiotic. J. Antimicrob. Agents Chemother. 27:517–526 (1991).
A. R. Gascon, B. Calvo, R.M. Hernandez, A. Dominguez-Gil, and J. L. Pedraz. Interspecies scaling of cimetidine-theophylline pharmacokinetic interaction: Interspecies scaling in pharmacokinetic interactions. Pharm. Res. 11:945–950 (1994).
R. L. Dedrick, K. B. Bischoff, and D. S. Zahardo. Interspecies correlation of plasma concentration history of methotrexate (NSC-740). Cancer Chemother. Rep. 54:95–101 (1970).
H. Boxenbaum and R. Ronfeld. Interspecies pharmacokinetic scaling and the Dedrick plots. Am. J. Physiol. 245:R768–R775 (1983).
R. M. J. Ings. Interspecies scaling and comparisons in drug development and toxicokinetics. Xenobiotica 20:1201–1231 (1990).
J. Mordenti and W. Chappell. The use of interspecies scaling in toxicokinetics. In A. Yacobi, J. P. Skelly, and V. K. Batra (eds.), Toxicokinetics and New Drug Development, Pergamon, New York, 1989, pp. 42–96.
F. A. A. Dallas, C. M. Dixon, R. J. McCulloch, and D. A. Saynor. Kinetics of 14CGR43175 in rat and dog. Cephalalgia Suppl. 9:53–56 (1989).
P. D. Andrew, H. L. Birch, and D. A. Phillpot. Determination of sumatriptan succinate in plasma and urine by high-performance liquid chromatography with electrochemical detection. J. Pharm. Sci. 82:73–76 (1993).
S. L. Beal and L. B. Sheiner (eds.). NONMEM Users Guides, NONMEM Project Group, University of California, San Francisco, 1992.
C. M. Dixon, D. A. Saynor, P. D. Andrew, J. Oxford, A. Bradbury, and M. H. Tarbit. Disposition of sumatriptan in laboratory animals and humans. Drug Metab. Dispos. 21:761–769 (1993).
L. F. Lacey, E. K. Hussey, and P. A. Fowler. Single dose pharmacokinetics of sumatriptan in healthy volunteers. Eur. J. Clin. Pharmacol. 47:543–548 (1995).
H. Boxenbaum. Interspecies scaling, allometry, physiological time, and the ground plan of pharmacokinetics. J. Pharmacokin. Biopharm. 10:201–227 (1982).
H. Boxenbaum. Interspecies variation in liver weight, hepatic blood flow, and antipyrine intrinsic ciearance: Extrapolation of data to benzodiazepines and phenytoin. J. Pharmacokin. Biopharm. 8:165–176 (1980).
H. Boxenbaum and R. W. D'Souza. Interspecies pharmacokinetic scaling, biological design and neoteny. Adv. Drug Res. 19:139–196 (1990).
H. Boxenbaum. Interspecies pharmacokinetic scaling and the evolutionary-comparative paradigm. Drug Metab. Rev. 15:1071–1121 (1984).
A. Puigdemont, J. Ramis, R. Guitart, and M. Arboix. Species scaling of propafenone disposition and concentration time relationships among eight mammalian species. J. Pharm. Sci. 82:1126–1129 (1993).
P. P. A. Humphrey, W. Feniuk, A. S. Marriott, R. J. N. Tanner, M. R. Jackson, and M. L. Tucker. Preclinical studies on the anti-migraine drug, sumatriptan. Eur. Neurol. 31:282–290 (1991).
C. A. Cruze, G. R. Kelm, and M. P. Meredith. Interspecies scaling of tebufelone pharmacokinetic data and application to preclinical toxicology. Pharm. Res. 12:895–901 (1995).
T. Lave, A. H. Schmitt-Hoffmann, P. Coassolo, B. Valles, G. Ubeaud, B. Ba, R. Brandt, and R. C. Chou. A new extrapolation method from animals to man: Application to a metabolized compound, mofarotene. Life Sci. 56:473–478 (1995).
J. Mordenti. Man versus beast: Pharmacokinetic scaling in mammals. J. Pharm. Sci. 75:1028–1040 (1986).
M. Leal, A. Yacobi, and V. K. Batra. Use of toxicokinetic principles in drug development: bridging preclinical and clinical studies. In A. Yacobi, J. P. Skelly, V. P. Shah, and L. Z. Benet (eds.), Integration of Pharmacokinetics, Pharmacodynamics, and Toxicokinetics in Rational Drug Development, Plenum Press, New York, 1993, pp. 7–13.
C. Efthymiopoulos, V. Cosson, and A. Bye. The use of NONMEM in the interspecies allometric scaling (Abstract). Second meeting of Page, London, June 1994.
T. Lave, B. Levet-Trafit, A. H. Schmitt-Hoffmann, B. Morgenroth, W. Richter, and R. C. Chou. Interspecies scaling of interferon disposition and comparison of allometric scaling with concentration time transformations. J. Pharm. Sci. 84:1285–1290 (1995).
G. Levy. The case for preclinical pharmacodynamics. In A. Yacobi, J. P. Skelly, V. P. Shah, and L. Z. Benet (eds.), Integration of Pharmacokinetics, Pharmacodynamics, and Toxicokinetics in Rational Drug Development, Plenum Press, New York, 1993, pp. 7–13.
D. Young, D. Piscitelli, B. Patel, and L. Fleisher. First dose in man (Abstract). Clin. Trials Metanaly. 29:247–308 (1994).
W. Weber, L. Harnisch, M. Zimmer, P. Crause, and B. Katgely. Optimization of a “First Dose in Man” Study using a NONMEM Model for Mammals (Abstract). Third meeting of Page, Frankfurt am Main, Germany, June 1995.
H. Boxenbaum and C. DiLea. First-time-in-human dose selection: Allometric thoughts and perspectives. J. Clin. Pharmacol. 35:957–966 (1995).
H. E. Connor, W. Feniuk, and P. P. A. Humphrey. Characterization of 5-HT receptors mediating contraction of canine and primate basilar artery by use of GR43175, a selective 5-HT1-like receptor agonist. Br. J. Pharmacol. 96:379–387 (1989).
G. Levy. The case for preclinical pharmacodynamics: Why and how? (Abstract). Therapie 49:289 (1994).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cosson, V.F., Fuseau, E., Efthymiopoulos, C. et al. Mixed Effect Modeling of Sumatriptan Pharmacokinetics During Drug Development. I: Interspecies Allometric Scaling. J Pharmacokinet Pharmacodyn 25, 149–167 (1997). https://doi.org/10.1023/A:1025728028890
Published:
Issue Date:
DOI: https://doi.org/10.1023/A:1025728028890