Abstract
The pharmacokinetic and pharmacodynamic profiles of intravenous trimazosin, a postsynaptic α 1 antagonist, were analyzed empirically by integrated modelling techniques. The mean terminal elimination half-life for trimazosin was 186± 80 min and the mean elimination half-life of its alkyl hydroxylated metabolite (CP23445) was 93± 29 min. The placebo-corrected fall in systolic blood pressure after 5 min standing was most appropriately characterized in all subjects by a model that incorporated “effect” compartments for both parent drug and its metabolite.
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J. Buyniski, A. W. Pircio, J. E. Schurig, and J. A. Campbell. Effect of Tiodazosin, Prazosin, Trimazosin, and Phentolamine on blood pressure, heart rate, and on pre and postsynaptic alpha-adrenergic receptors in the rat.Clin. Exp. Hypertension 2:1039–1045 (1980).
J. W. Constantine and H. J. Hess. The cardiovascular effects of trimazosin.Eur. J. Pharmacol. 74:227–235 (1981).
H. L. Elliott, J. Vincent, C. B. Lawrie, M. A. Hughes, P. A. Meredith, and J. L. Reid. Trimazosin: a clinical pharmacological evaluation.Clin. Pharmacol Ther. (in press).
H. L. Elliott, P. A. Meredith, D. J. Sumner, K. McLean, and J. L. Reid. A pharmacodynamic and pharmacokinetic assessment of a newα adrenoceptor antagonist, doxazosin (UK33274) in normotensive subjects.Br. J. Clin. Pharmacol. 13:699–703 (1982).
Pfizer Central Research, personal communication.
L. B. Sheiner, D. R. Stanski, S. Vozeh, R. D. Miller, and J. Ham. Simultaneous modelling of pharmaco-kinetics and pharmacodynamics: application to d-tubocurarine.Clin. Pharmacol. Ther. 25:358–371 (1979).
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).
A. W. Kelman and B. Whiting. Modelling of drug responses in individual subjects.J. Pharmacokin. Biopharm. 8:115–130 (1980).
B. Whiting, A. W. Kelman, J. Barclay, and G. J. Addis. Modelling theophylline response in individual patients with chronic bronchitis.Br. J. Clin. Pharmacol. 12:481–488 (1981).
M. A. Hughes, P. A. Meredith, and H. L. Elliott. The determination of trimazosin and its metabolite (CP23445) in whole blood by high performance liquid chromatography.J. Pharmacol. Methods (in press).
P. R. Bevington.Data Reduction and Error Analysis for the Physical Sciences. McGrawHill, New York, 1969, pp. 235–236.
H. G. Boxenbaum, S. Riegelman, and R. M. Elashoff. Statistical estimations in pharmcokinetics.J. Pharmacokin. Biopharm. 2:123–148 (1974).
H. Akaike. A new look at the statistical model identification.IEEE Trans. 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. Draper and H. Smith.Applied Regression Analysis. Wiley, New York, 1966, pp. 8–99.
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Meredith, P.A., Kelman, A.W., Elliott, H.L. et al. Pharmacokinetic and pharmacodynamic modelling of trimazosin and its major metabolite. Journal of Pharmacokinetics and Biopharmaceutics 11, 323–335 (1983). https://doi.org/10.1007/BF01058953
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DOI: https://doi.org/10.1007/BF01058953