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Vol. 289, Issue 1, 224-230, April 1999
Department of Pharmacology and Pharmaceutics, We kinetically analyzed the disposition of L-carnitine of
juvenile visceral steatosis (JVS) mice compared with that of normal mice to elucidate the mechanism of the systemic L-carnitine
deficiency of JVS mice. There were significant differences in the
plasma concentration-time course of total radioactive carnitine
(L-[3H]carnitine,
[acetyl-3H]carnitine, and other
[acyl-3H]carnitines) between normal and
JVS mice after a single i.v. or p.o. administration of
L-[3H]carnitine (250 ng/kg). The oral
bioavailability of L-[3H]carnitine in JVS
mice (0.341) was about half of that in normal mice (0.675). The
cumulative urinary excretion of total radioactive carnitine in JVS mice
was about 10-fold more than that in normal mice, and the total
clearance of unchanged L-[3H]carnitine for
JVS mice (6.70 ml/min) was significantly higher than that for normal
mice (2.45 ml/min). The distribution volume at the steady state of
unchanged L-[3H]carnitine in JVS mice (1.10 liters/kg) was significantly smaller than that in normal mice (8.16 liters/kg). At 4 h after an i.v. administration, the apparent
tissue-to-plasma concentration ratios of unchanged
L-[3H]carnitine for various tissues of JVS
mice, except for brain, were about one half to one 20th of those in
normal mice. In conclusion, this in vivo disposition kinetic study of
L-carnitine supports the previous in vitro finding that the
L-carnitine transporter is absent or functionally deficient
in JVS mice because the renal reabsorption, the intestinal absorption,
and the apparent tissue-to-plasma concentration ratios in JVS mice are
significantly lower than those in normal mice. The JVS mouse should be
a useful experimental model for studying carnitine deficiency diseases.
0022-3565/99/2891-0224$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics
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