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The relationship between the pharmacokinetics of amrinone in the marmoset and platelet effects

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Summary

The pharmacokinetic characteristics of amrinone have been studied in six female marmosets following oral administration of 1, 12.5, 25, 50 and 75 mg.kg−1 and an intravenous dose of lmg.kg−1. The mean plasma AUG)0 ∞ was determined at each dose level; the values obtained were 2.5, 18.7, 33.9, 103 and 312 μ.h.ml−1 for the oral doses of 1. 12.5, 25, 50 and 75 mg.kg−1 respectively and 1.9 μ.h.ml−1 for the intravenous dose of lmg.kg−1 Mean maximum observed plasma concentrations were 0.6, 7.1, 11.7, 23.7 and 40.0 μg.ml−1 respectively following oral doses. Over the range 1 to 50 mg.kg0 ∞ the AUCooe was linear; at 75 mg.kg−1 the AUCo0 8 was disproportionately greater. Elimination appeared to be first order over the dose range 1 to 50 mg.kg−1 and the 11/2 in the marmoset was approximately 1 to 3 hours over this dose range. The plasma levels achieved arc discussed in relation to the observed effects on the platelet population in this species following chronic administration at high dose levels.

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Authors and Affiliations

  1. Toxicology Department, Sterling-Winthrop Research Centre, NE66 2IH, Alnwick, Northumberland, UK

    C. T. Eason, J. I. Usansky, G. P. Henry, P. Powles & F. W. Bonner

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  1. C. T. Eason
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  2. J. I. Usansky
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  3. G. P. Henry
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  4. P. Powles
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  5. F. W. Bonner
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Eason, C.T., Usansky, J.I., Henry, G.P. et al. The relationship between the pharmacokinetics of amrinone in the marmoset and platelet effects. European Journal of Drug Metabolism and Pharmacokinetics 13, 129–133 (1988). https://doi.org/10.1007/BF03191314

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