The nephroprotective effect of betamipron (200 mg/kg) was evaluated after i
ntravenous administration of a high dose of DA-1131 (200 mg/kg) to rabbits.
Extensive tubular necrosis was observed without betamipron but the necrosi
s was not observed with betamipron at 8 h after intravenous administration
of DA-1131 based on kidney microscopy. By treatment with betamipron, the am
ounts and tissue to plasma (TIP) ratios of DA-1131 in renal cortex and whol
e kidney decreased significantly (65-91% decrease) at both 30 min and 2 h a
fter intravenous administration of the drug to rabbits. This indicated that
the accumulation of DA-1131. in rabbit renal cortex and whole kidney was i
nhibited by betamipron. This resulted in significantly greater percentages
of intravenous DA-1131 excreted in urine as unchanged drug, 60.9 versus 40.
1%, and significantly faster rend clearance (Cl-r) of DA-1131 (6.10 versus
3.22 mL/min/kg) by treatment with betamipron. By treatment with betamipron,
the amounts and T/P ratios of DA-1131 in renal cortex and whole kidney dec
reased significantly from 30 min and the renal function remained intact at
8 h after intravenous administration of DA-1131. The above data suggested t
hat the nephroprotective effect of betamipron was fast and persisted for a
long period of time in rabbits. Copyright (C) 1999 John Wiley & Sons, Ltd.