Abstract
A pharmacokinetic model incorporating 14 compartments and 29 transfer coefficients has been developed from experimental data obtained after intravenous administration of a single dose to describe the distribution of doxantrazole in the rat. The distribution calculated from the model agreed closely with that determined experimentally. In addition, the model was able to predict with considerable accuracy the distribution of doxantrazole after repeated dosing.
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References
C. D. Thron. Linearity and superposition in pharmacokinetics.Pharmacol. Rev. 26:3–31 (1974).
T. Teorell. Kinetics of distribution of substances administered to the body. I. The extravascular modes of administration.Arch. Int. Pharmacodyn. 57:205–225 (1937).
T. Teorell. Kinetics of distribution of substances administered to the body. II. The intravascular modes of administration.Arch. Int. Pharmacodyn. 57:226–240 (1937).
K. B. Bischoff, R. L. Dedrick, D. S. Zaharko, and J. A. Longstreth. Methotrexate pharmacokinetics.J. Pharm. Sci. 60:1128–1132 (1971).
K. J. Himmelstein and K. B. Bischoff. Mathematical representations of cancer chemotherapy effects.J. Pharmacokin. Biopharm. 1:51–68 (1973).
K. J. Himmelstein and K. B. Bischoff. Models of ara-C chemotherapy in L1210 leukemia in mice.J. Pharmacokin. Biopharm. 1:69–81 (1973).
M. Weatherall and R. Williams. Quantitative treatment of the distribution of drugs after intravenous injection.Br. J. Pharmacol. 39:234P-235P (1970).
J. F. Batchelor, M. J. Follenfant, L. G. Garland, J. H. Gorvin, A. F. Green, H. F. Hodson, D. T. D. Hughes, and J. E. Tateson. Doxantrazole. an antiallergic agent orally effective in man.Lancet 1:1169–1170 (1975).
J. A. Jacquez.Compartmental Analysis in Biology and Medicine, Elsevier, London, 1972, pp. 31–35.
R. Fletcher.An Efficient Globally Convergent Algorithm for Unconstrained and Linearly Constrained Optimisation Problems, A.E.R.E., TP. 431, Atomic Energy Research Establishment, Harwell, U.K., 1970.
P. Johnson, P. A. Rising, and T. J. Rising. Liquid scintillation counting of biological samples using external standardisation and automatic data processing. In M. A. Crooks, P. Johnson, and B. Scales (eds),Liquid Scintillation Counting, Vol. 2, Heyden and Sons Ltd., London, 1972, pp. 267–277.
M. S. Patterson and R. C. Greene. Measurement of low energy beta-emitters in aqueous solution by liquid scintillation counting of emulsions.Anal. Chem. 37:854–857 (1965).
M. H. Griffiths and A. Mallinson. A furnace for combustion of biological material containing tritium and carbon-14 labelled compounds.Anal. Biochem. 22:465–473 (1968).
J. Dent and P. Johnson. Solubilisation of mammalian tissues for scintillation counting. In M. A. Crooks and P. Johnson (eds),Liquid Scintillation Counting, Vol. 3, Heyden and Sons Ltd., London, 1973, pp. 122–131.
H. H. Donaldson (ed.).The Rat: Data and Reference Tables, 2nd ed., Wistar Institute of Anatomy and Biology, Philadelphia, 1924.
W. S. Spector (ed.).Handbook of Biological Data, Saunders, Philadelphia, 1956.
A. Bye and G. Land. Determination of 3-(5-tetrazolyl)thioxanthane 10,10-dioxide in human plasma, urine and feces.J. Chromatog. 115:93–99 (1975).
H. Eriksson, W. Hellström, and å. Ryrfeldt. The biliary excretion of3H-inulin and3H-terbutaline in the unanaesthetised rat.Acta Physiol. Scand. 95:1–5 (1975).
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Caldwell, I.C., Mahmood, S. & Weatherall, M. Mathematical prediction of drug distributionin vivo: Studies with doxantrazole in rats. Journal of Pharmacokinetics and Biopharmaceutics 6, 521–537 (1978). https://doi.org/10.1007/BF01062107
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DOI: https://doi.org/10.1007/BF01062107