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雄性犬口服番茄红素后的药代动力学及组织分布

Pharmacokinetics and tissue distribution of orally administered lycopene in male dogs.

作者信息

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

机构信息

Toxicology Research Laboratory, University of Illinois at Chicago, Chicago, IL, USA.

出版信息

J Nutr. 2003 Sep;133(9):2788-92. doi: 10.1093/jn/133.9.2788.

Abstract

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-)( infinity ), 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.

摘要

番茄红素是番茄及番茄制品中的主要类胡萝卜素,摄入番茄红素与降低前列腺癌风险相关。本研究的目的是测定雄性犬口服番茄红素后的药代动力学和组织分布。给2只犬/剂量分别单次口服10、30和50 mg/kg体重(BW)的番茄红素后,平均半衰期为36小时,30和50 mg/kg BW剂量后的血浆全身暴露水平(曲线下面积AUC(0-)( infinity))相似。在重复给药研究中,6只犬口服30 mg/(kg BW·d),持续28天,导致血浆中番茄红素的稳态浓度在785至997 nmol/L之间。表观清除率、分布容积和表观消除半衰期分别为2.29 L/(h·kg)、96 L/kg和30.5小时。在最后一剂后1或5天处死犬,收集23种组织进行番茄红素分析。番茄红素浓度在肝脏、肾上腺、脾脏、淋巴结和肠道组织中最高。停止治疗后1天和5天,肝脏中的番茄红素浓度分别为66和91 nmol/g。给药停止后1天和5天,前列腺中的番茄红素浓度均<0.2 nmol/g(<肝脏浓度的0.4%)。尽管给药材料中使用的是70%的反式番茄红素,但在血浆和组织中鉴定出的大多数番茄红素是顺式番茄红素。

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