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

Veda Diwadkar-Navsariwala, Janet A. Novotny, David M. Gustin, Jeffery A. Sosman, Keith A. Rodvold, James A. Crowell, Maria Stacewicz-Sapuntzakis, Phyllis E. Bowen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1927-1939
Number of pages13
JournalJournal of lipid research
Volume44
Issue number10
DOIs
StatePublished - Oct 2003

Keywords

  • Carotenoids
  • Human study
  • Lycopene disposition
  • Physiological model
  • Tissue distribution
  • WinSAAM

ASJC Scopus subject areas

  • Endocrinology
  • Biochemistry
  • Cell Biology

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