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Nutrient Metabolism

Pharmacokinetics and Tissue Distribution of Orally Administered Lycopene in Male Dogs

Peter J. Korytko^*,1, Keith A. Rodvold, James A. Crowell^**, Maria Stacewicz-Sapuntzakis, Veda Diwadkar-Navsariwala, Phyllis E. Bowen, Wolfgang Schalch and Barry S. Levine^*

^* Toxicology Research Laboratory, University of Illinois at Chicago, Chicago, IL; Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL; ^** National Cancer Institute, Rockville, MD; Human Nutrition, University of Illinois at Chicago, Chicago, IL; and Roche Vitamins Inc, Basel, Switzerland

¹To whom correspondence should be addressed. E-mail: peter.j.korytko{at}pfizer.com.

Consumption of lycopene, the predominant carotenoid in tomatoes and tomato products, is associated with reduced prostate cancer risk. The purpose of this study was to measure the pharmacokinetics and tissue distribution of lycopene after oral administration to male dogs. After single doses of 10, 30 and 50 mg/kg body weight (BW) lycopene to 2 dogs/dose, the mean half-life was 36 h and the plasma systemic exposure levels (AUC_0-, area under the curve) after the 30 and 50 mg/kg BW doses were similar. In a repeat dose study, 30 mg/(kg BW · d) administered orally to six dogs for 28 d resulted in steady-state plasma concentrations between 785 and 997 nmol/L lycopene. Apparent clearance, volume of distribution and apparent elimination half-life were 2.29 L/(h · kg), 96 L/kg and 30.5 h, respectively. Dogs were killed 1 or 5 d after the last dose and 23 tissues were collected for lycopene analysis. Lycopene concentrations were highest in liver, adrenals, spleen, lymph nodes and intestinal tissues. Liver lycopene concentrations were 66 and 91 nmol/g 1 and 5 d after cessation of treatment, respectively. Prostate lycopene concentrations were < 0.2 nmol/g both 1 and 5 d after dosing ceased (<0.4% of liver concentrations). Although 70% trans-lycopene was used in the dosing material, most of the lycopene identified in plasma and tissues was cis-lycopene.

KEY WORDS: • carotenoid • prostate • cancer • chemoprevention • canine

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