Abstract
Pharmacokinetic and drug response data from individual subjects are analyzed empirically by two different mathematical techniques. The drugs involved are the antiarrhythmic agent disopyramide, whose kinetics can be described by a two-compartment model, and two cardiac glycosides, digoxin and β-methyl digoxin, for which three-compartment models are appropriate. The first analytical approach uses multiple linear regression to describe response in terms of the amount of drug in several kinetic compartments. The second approach describes response in terms of the drug concentration in an “effect” compartment. Both approaches describe the data equally well and require the same number of parameters for model specification.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
W. G. Kramer, A. J. Kolibash, R. P. Lewis, M. S. Bathala, J. A. Visconti, and R. H. Reuning. Pharmacokinetics of digoxin: Relationship between response intensity and predicted compartmental drug levels in man.J. Pharmacokin. Biopharm. 7:47–61 (1979).
S. M. Bryson, B. Whiting, and J. R. Lawrence. Disopyramide, serum and pharmacologic effect kinetics applied to the assessment of bioavailability.Br. J. Clin. Pharmacol. 6:409–419 (1978).
B. Whiting, N. H. G. Holford, and L. B. Sheiner. Quantitative analysis of the disopyramide concentration-effect relationship.Br. J. Clin. Pharmacol. 9:67–75 (1980).
P. J. Meffin, R. A. Winkle, and T. F. Blaschke. Response optimization of drug dosage: Antiarrhythmic studies with tocainide.Clin. Pharmacol. Ther. 22:42–57 (1977).
L. B. Sheiner, D. R. Stanski, S. Vozeh, R. D. Miller, and J. Ham. Simultaneous modelling of pharmacokinetics and pharmacodynamics: Application tod-tubocurarine.Clin. Pharmacol. Ther. 25:358–371 (1979).
R. L. Galeazzi, L. Z. Benet, and L. B. Sheiner. Relationship between the pharmacokinetics and pharmacodynamics of procainamide.Clin. Pharmacol. Ther. 20:278–289 (1976).
A. W. Kelman, D. J. Sumner, M. Lonsdale, J. R. Lawrence, and B. Whiting. Comparative pharmacokinetics and pharmacodynamics of cardiac glycosides.Br. J. Clin. Pharmacol. (in press).
J. Neter and W. Wasserman.Applied Linear Statistical Models, Richard D. Irwin, Inc., Homewood, Ill., 1974, pp. 87–89.
P. R. Bevington.Data Reduction and Error Analysis for the Physical Sciences, McGraw-Hill, New York, 1969, pp. 235, 236.
H. Akaike, A new look at the statistical model identification.IEEE Tr. Automat. Contr. 19:716–723 (1973).
H. Akaike. An information criterion (AIC)Math. Sci. 14:5–9 (1976).
K. Yamaoka, T. Nakagawa, and T. Uno. Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations.J. Pharmacokin. Biopharm. 6:165–176 (1978).
N. R. Draper and H. Smith.Applied Regression Analysis, J. Wiley, New York, 1966, pp. 86–99.
D. J. Sumner, A. J. Russell, and B. Whiting. Digoxin pharmacokinetics: Multicompartmental analysis and its clinical implications.Br. J. Clin. Pharmacol. 3:221–229 (1976).
J. L. Cunningham, D. D. Shen, I. Shudo, and D. L. Azarnoff. The effect of nonlinear disposition kinetics on the systemic availability of disopyramide.Br. J. Clin. Pharmacol. 5:343–346 (1978).
P. J. Meffin, E. W. Robert, R. A. Winkle, S. Harapat, F. A. Peters, and D. C. Harrison. Role of concentration-dependent plasma protein binding in disopyramide disposition.J. Pharmacokin. Biopharm. 1:29–46 (1979).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kelman, A.W., Whiting, B. Modeling of drug response in individual subjects. Journal of Pharmacokinetics and Biopharmaceutics 8, 115–130 (1980). https://doi.org/10.1007/BF01065188
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF01065188