A physiological pharmacokinetic model describing the disposition of lycopene in healthy men.
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.
Diwadkar-Navsariwala
Veda
V
Department of Human Nutrition, University of Illinois at Chicago, Chicago, IL 60612, USA.
Novotny
Janet A
JA
Gustin
David M
DM
Sosman
Jeffery A
JA
Rodvold
Keith A
KA
Crowell
James A
JA
Stacewicz-Sapuntzakis
Maria
M
Bowen
Phyllis E
PE
D000328:Adult; D016588:Anticarcinogenic Agents / Q000097:blood / Q000493:pharmacokinetics*; D000975:Antioxidants / Q000493:pharmacokinetics*; D001628:Beverages; D002338:Carotenoids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004032:Diet; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D000077276:Lycopene; D018551:Solanum lycopersicum; D008297:Male; D008875:Middle Aged; D000069463:Olive Oil; D010938:Plant Oils; D014018:Tissue Distribution; D014815:Vitamins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D008055:Lipids; D000069463:Olive Oil; D010938:Plant Oils; D014815:Vitamins; D002338:Carotenoids; D000077276:Lycopene