Disposition kinetics of [alpha]-tocopherol in apolipoprotein B knockout mice

• Published in: Pharmaceutical research Vol. 20; no. 3; p. 368
• Main Authors: Yokogawa, Koichi, Shima, Yuichiro, Hashimoto, Tomoka, Hiyajyo, Makoto
• Format: Journal Article
• Language: English
• Published: New York Springer Nature B.V 01.03.2003
• ISSN: 0724-8741; 1573-904X

We examined the effects of apolipoprotein B (apoB) on the disposition kinetics of alpha-tocopherol by using apoB knockout mice. The concentrations of alpha-tocopherol in plasma and tissues were measured by gas chromatography-mass spectrometry. In apob (-/-) mice, the endogenous levels of alpha-tocopherol in plasma and tissues (except liver) were significantly lower, and the liver concentration was significantly higher than those in wild-type mice. After single i.v. administration of alpha-tocopherol (25 mg/kg), the area under the plasma concentration-time curve (AUC) and the distribution volume at steady state were significantly decreased, whereas the total clearance of alpha-tocopherol was significantly increased in apob (-/-) vs. wild-type mice. Alpha-Tocopherol was highly distributed to the liver, compared with other tissues. After an oral administration of alpha-tocopherol (100 mg/kg), the intestinal absorption of alpha-tocopherol was very low in apoB knockout mice, as the value of AUC0-32h for apob (-/-) mice (17.7 +/- 8.3 (microg h/mL) was significantly less than that for apob (+/+) wild-type mice (96.5 +/- 15.8 microg h/mL, mean +/- SD of five experiments, p < 0.01). The biliary excretion of alpha-tocopherol was significantly greater in apob (+/-) mice than in apob (+/+) mice. These results show that apoB plays a role in hepatic secretion and intestinal absorption of alpha-tocopherol.