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Research ArticleArticle

Influence of Two Commercial Fibers in the Pharmacokinetics of Ethinylestradiol in Rabbits

N. Fernández, M. J. Diez, M. T. Terán, J. J. García, A. P. Calle and M. Sierra
Journal of Pharmacology and Experimental Therapeutics August 1998, 286 (2) 870-874;
N. Fernández
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M. J. Diez
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M. T. Terán
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J. J. García
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A. P. Calle
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M. Sierra
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Abstract

Fiber formulations are used in human nutrition owing to their beneficial properties for health. It is probable that ingestion of fiber coincides with the oral administration of drugs, and a modification of its oral absorption, and therefore of its pharmacokinetics, can appear. In the present study, the compartmental and noncompartmental pharmacokinetic parameters of ethinylestradiol (EE) in rabbits after oral administration were determined. It was also studied whether the presence of two different fiber formulations [A, wheat bran (76.5%), fruit fiber (12%) and guar gum (2%) and B,Plantago ovata seeds (65%) and P. ovataseed cuticles (2.2%)] in the gastrointestinal tract modified the pharmacokinetics of EE when administered at the same time. Three groups of rabbits were used: control, fiber A and fiber B. The animals in all three groups received 1 mg/kg b. wt. EE. The estrogen was administered alone in the control group and in the presence of 4 g of fiber A and fiber B, respectively, in the other two groups. After compartmental (two-compartment open model) and noncompartmental analyses of plasma concentrations, statistical analysis revealed that the presence of fiber (both A and B) decreased between 29% and 35% the extent of EE absorbed (represented by the pharmacokinetic parameters area under the curve and the maximum plasma concentration) without affecting the rate of the absorption process (represented by the time to reach maximum concentration and the absorption rate constant).

Footnotes

  • Send reprint requests to: Nélida Fernández, Department of Physiology, Pharmacology and Toxicology, Campus Vegazana s/n, University of Leon, 24071-Leon, Spain.

  • Abbreviations:
    EE
    ethinylestradiol SHBG, sex hormone-binding globulin
    α and β
    apparent first-order disposition rate constants
    A and B
    α and β zero-time intercepts, respectively
    ka
    absorption rate constant
    k10
    apparent first-order elimination rate constant from the central compartment
    k12
    apparent first-order transfer rate constant from the central compartment to the peripheral compartment
    k21
    apparent first-order transfer rate constant from the peripheral compartment to the central compartment
    AUC
    area under the plasma concentration-time curve
    Cmax
    maximum plasma concentration
    tmax
    time to reach maximum concentration
    t1/2α
    half-life associated with α-phase
    t1/2β
    half-life associated with β-phase
    t1/2ka
    absorption half-life
    t1/2k10
    elimination from the central compartment half-life
    λ
    noncompartmental apparent first-order disposition rate constant
    t1/2λ
    half-life associated with λ phase
    AUCt−∞
    AUC from the last experimental time to infinity
    • Received November 5, 1997.
    • Accepted April 8, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 286, Issue 2
1 Aug 1998
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Research ArticleArticle

Influence of Two Commercial Fibers in the Pharmacokinetics of Ethinylestradiol in Rabbits

N. Fernández, M. J. Diez, M. T. Terán, J. J. García, A. P. Calle and M. Sierra
Journal of Pharmacology and Experimental Therapeutics August 1, 1998, 286 (2) 870-874;

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Research ArticleArticle

Influence of Two Commercial Fibers in the Pharmacokinetics of Ethinylestradiol in Rabbits

N. Fernández, M. J. Diez, M. T. Terán, J. J. García, A. P. Calle and M. Sierra
Journal of Pharmacology and Experimental Therapeutics August 1, 1998, 286 (2) 870-874;
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