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J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M300130-JLR200 on July 16, 2003

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Journal of Lipid Research, Vol. 44, 1927-1939, October 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

A physiological pharmacokinetic model describing the disposition of lycopene in healthy men

Veda Diwadkar-Navsariwala*, Janet A. Novotny§, David M. Gustin**, Jeffery A. Sosman{dagger}{dagger}, Keith A. Rodvold{dagger}, James A. Crowell§§, Maria Stacewicz-Sapuntzakis* and Phyllis E. Bowen1,*

* Departments of Human Nutrition, University of Illinois at Chicago, Chicago, IL 60612
{dagger} Pharmacy Practice, University of Illinois at Chicago, Chicago, IL 60612
§ Diet & Human Performance Laboratory, Beltsville Human Nutrition Research Center, Agriculture Research Service, United States Department of Agriculture, Beltsville, MD 20705
** Division of Hematology-Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637
{dagger}{dagger} Division of Hematology-Oncology, Department of Medicine, Vanderbilt University, Nashville, TN 37235
§§ Division of Cancer Prevention, National Cancer Institute, Rockville, MD 20892

1 To whom correspondence should be addressed. e-mail: pbowen{at}uic.edu

A physiological pharmacokinetic model was developed to describe the disposition of lycopene, delivered as a tomato beverage formulation in five graded doses (10, 30, 60, 90, or 120 mg), for a phase I study in healthy male subjects (five per dose). Blood was collected before dose administration (0 h) and at scheduled intervals until 672 h. Serum concentrations of carotenoids and vitamins were measured by high performance liquid chromatography analysis. The model was comprised of seven compartments: gastrointestinal tract, enterocytes, chylomicrons, plasma lipoproteins, fast-turnover liver, slow-turnover tissues, and a delay compartment before the enterocytes. As predicted, the percent absorption at the 10 mg dose (33.9 ± 8.1%) was significantly greater than at the higher doses; however, the amount of lycopene absorbed (mg) was not statistically different (mean: 4.69 ± 0.55 mg) between doses, suggesting a possible saturation of absorptive mechanisms.

The slow-turnover tissue compartment served as a slow-depleting reservoir for lycopene, and the liver represented the fast-turnover pool. Independent of dose, 80% of the subjects absorbed less than 6 mg of lycopene. This may have important implications for planning clinical trials with pharmacological doses of lycopene in cancer control and prevention if absorption saturation occurs at levels that are already being consumed in the population.

Supplementary key words lycopene disposition • carotenoids • physiological model • WinSAAM • human study • tissue distribution


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