Abstract
A mathematical treatment of the influence of sampling on drug kinetics in liver perfusion is presented. Based on the derived equations, a Fortran IV computer program (PERFUS) is given, by which the time course of drug concentrations can be simulated for any sampling scheme. The simulations show that the withdrawal of large samples from the reservoir, i.e., larger than 5% of the reservoir volume, results in substantially biased parameters for drugs that are rapidly distributed and/or metabolized. For the fitting of empirical data, a Fortran IV computer program is given, based on BMDX85 nonlinear least squares by Gauss-Newton iterations. This program (PERFIT) estimates model parameters corrected as if no sampling had occurred, no matter how distorted the drug disappearance curve mày be as a result of sampling or due to degeneration of the two-compartment model into a one-compartment model. The conditions under which this degeneration occurs are discussed.
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References
B. D. Ross.Perfusion Techniques in Biochemistry, Oxford University Press, London, 1972, p. 110.
R. Nagashima, G. Levy, and E. J. Sarcione. Comparative pharmacokinetics of coumarin anticoagulants. III.J. Pharm. Sci. 57:1881–1888 (1968).
M. Rowland, L. Z. Benet, and G. G. Graham. Clearance concepts in pharmacokinetics.J. Pharmacokin. Biopharm. 1:123–136 (1973).
H. de Nijs and C. J. Timmer. Pharmacokinetics of Org GB 94 (mianserin) in the isolated perfused rat liver and in the anaesthesized rat. Seventeenth Dutch Federative Meeting, Amsterdam, Abstracts Symposia and Communications, p. 312 (1976).
J. Vink, J. J. de Ridder, C. J. Timmer, and H. de Nijs. Mass spectrometry applied to metabolism studies of Org GC 94, a new anti-migraine drug. International Symposium on Mass Spectrometry in Drug Metabolism, June 1976, Milan, Italy.
R. I. Jennrich and P. F. Sampson. Application of stepwise regression to non-linear least squares estimation.Technometrics 10:63–72 (1968).
J. Myhill. Investigation of data error in the analysis of biological tracer data from three-compartment systems.J. Theor. Biol. 23:218–231 (1968).
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Timmer, C.J., Wijnand, H.P. Influence of sampling on drug kinetics in liver perfusion. Journal of Pharmacokinetics and Biopharmaceutics 5, 335–358 (1977). https://doi.org/10.1007/BF01061695
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DOI: https://doi.org/10.1007/BF01061695