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

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 slowturnover tissue compartment served as a slow-depleting reservoir for lycopene, and the liver represented the fastturnover 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, V., J. A.

Supplementation with the antioxidant lycopene significantly decreases oxidative stress parameters and the bone resorption marker N-telopeptide of type I collagen in postmenopausal women

“…The fact that consumption of all three forms of lycopene supplementation gave similar AUC values suggests that there is a maximum absorption concentration of lycopene at which saturation occurs, this is supported by other studies [32,33]. Our findings also demonstrated that serum lycopene did not increase further between 2 and 4 months of supplementation, which is supported by other intervention studies in which peak lycopene concentrations have been reported as early as 1-2 weeks after the beginning of supplementation [34].…”

Lycopene has limited effect on cell proliferation in only two of seven human cell lines (both cancerous and noncancerous) in an in vitro system with doses across the physiological range

“…Human subjects had a plasma increase of 0.47-0.58 μM after two weeks with a 25 mg supplement/day of lycopene or tomato paste (Richelle et al, 2002). Other researchers reported a serum concentration of 0.34-0.65 μM after dosing with 10 to 120 mg/day of lycopene with a peak serum concentration two days after the dose was given (Diwadkar-Navsariwala et al, 2003).…”

“…The dose range used was 100X higher to 10X lower than the normal physiological concentrations of lycopene in various tissues (Diwadkar-Navsariwala et al, 2003;van Breeman et al, 2002).…”

“…The physiological level of lycopene in human blood and tissues varies with intake and tissue type (Diwadkar-Navsariwala et al, 2003;van Breeman et al, 2002). Lycopene in human blood averages ~0.5 μM of plasma and tissue levels vary from 0.001 μM wet weight in adipose tissue to 0.02 μM wet weight in adrenals and testes (Stahl and Sies, 1996).…”

Overview of carotenoid bioavailability determinants: From dietary factors to host genetic variations

“…This saturation of the 350 absorptive capacity has been reported for lycopene (Diwadkar-Navsariwala, et al, 2003). This factor is considered to be the key factor governing carotenoid bioavailability 355 because, to be absorbed, carotenoids first need to be extracted from their food matrix and to 356 be incorporated into mixed micelles in the upper part of the digestive tract.…”