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
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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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