Disposition kinetics of alpha-tocopherol in apolipoprotein B knockout mice.
OBJECTIVE
We examined the effects of apolipoprotein B (apoB) on the disposition kinetics of alpha-tocopherol by using apoB knockout mice.


METHODS
The concentrations of alpha-tocopherol in plasma and tissues were measured by gas chromatography-mass spectrometry.


RESULTS
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.


CONCLUSIONS
These results show that apoB plays a role in hepatic secretion and intestinal absorption of alpha-tocopherol.
Yokogawa
Koichi
K
Department of Hospital Pharmacy, School of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
Shima
Yuichiro
Y
Hashimoto
Tomoka
T
Hiyajyo
Makoto
M
Kadoyama
Kaori
K
Ishizki
Junko
J
Nomura
Masaaki
M
Miyamoto
Ken-ichi
K
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001055:Apolipoproteins B / Q000235:genetics*; D019540:Area Under Curve; D001646:Bile / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013997:Time Factors; D014018:Tissue Distribution; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000975:Antioxidants; D001055:Apolipoproteins B; D024502:alpha-Tocopherol