Abstract
Interspecies correlations of pharmacokinetic parameters obtained in animals were used to predict human pharmacokinetics in order to design the first clinical study of an investigational drug. The serum pharmacokinetics of aztreonam, a novel monocyclic beta-lactam antibiotic, were described for mice, rats, rabbits, and monkeys, using serum clearance and apparent volume of distribution. A one-compartment pharmacokinetic model yielded predictions for aztreonam clinical pharmacokinetics that were very helpful in choosing doses and serum sampling times for the first kinetic study in healthy male volunteers. Predicted serum aztreonam concentrations agreed well with subsequently measured values in man.
Similar content being viewed by others
References
H. Boxenbaum. Interspecies scaling, allometry, physiological time, and the ground plan of pharmacokinetics.J. Pharmacokin. Biopharm. 10:201–227 (1982).
M. Weiss, W. Sziegoleit, and W. Forester. Dependence of pharmacokinetic parameters on the body weight.Int. J. Pharmacol. 15:572–575 (1977).
R. L. Dedrick, K. B. Bischoff, and D. S. Zaharko. Interspecies correlation of plasma concentration history of methotrexate (NSC-740).Cancer Chemother. Rep. Part I 54:95–101 (1970).
R. L. Dedrick. Animal scale-up.J. Pharmacokin. Biopharm. 1:435–461 (1973).
H. Aoki, H. Sakai, M. Kohsaka, T. Konomi, J. Hosoda, Y. Kubochi, and E. Iguchi. Nocardicin A, a new monocydic β-lactam antibiotic. I. Discovery, isolation and characterization.J. Antibiotics 19:492–500 (1976).
E. A. Swabb, M. A. Leitz, F. G. Pilkiewicz, and A. A. Sugerman. Pharmacokinetics of the monobactam SQ 26,776 after single intravenous doses in healthy subjects.J. Antimicrob. Chemother. 8 (Suppl. E):131–140 (1981).
L. Z. Benet and R. L. Galeazzi. Noncompartmental determination of the steady-state volume of distribution.J. Pharm. Sci. 68:1071–1074 (1979).
D. Perrier and M. Mayersohn. Noncompartmental determination of the steady-state volume of distribution for any mode of administration.J. Pharm. Sci. 71:372–373 (1982).
T. Colton.Statistics in Medicine. Little, Brown, Boston, 1974, p. 212.
M. Gibaldi and D. Perrier.Pharmacokinetics. Marcel Dekker, New York, 1975, p. 2.
D. P. Bonner, R. R. Whitney, C. O. Baughn, B. H. Miller, S. J. Olsen, and R. B. Sykes. In-vivo properties of SQ 26,776.J. Antimicrob. Chemother. 8(Suppl. E):123–130 (1981).
E. A. Swabb, A. A. Sugerman, and D. N. McKinstry. Multiple-dose pharmacokinetics of the monobactam, aztreonam (SQ 26,776), in healthy subjects.Antimicrob. Agents Chemother. 23:125–132 (1983).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Swabb, E.A., Bonner, D.P. Prediction of aztreonam pharmacokinetics in humans based on data from animals. Journal of Pharmacokinetics and Biopharmaceutics 11, 215–223 (1983). https://doi.org/10.1007/BF01061865
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF01061865