Effects of multiple
oral administration of
enprostil ((+/-)-11 alpha,15 alpha-dihydroxy-9-oxo-16-phenoxy-17,18,19,20-tetranorprosta- 4,5,13(t)-trienoic
acid methyl
ester, TA 84135) (20 micrograms/kg/d) and its
solvent propylene carbonate (PC, 100 microliters/kg/d) on
body weight gain, liver weight, hepatic
drug metabolizing
enzyme system and
hexobarbital sleeping time were investigated in male rats during a 14-day period.
Cytochrome P-450 content (as compared to the untreated control) and
cytochrome b5 content (as compared to PC treated group) were slightly, but significantly, reduced in the group given a single oral dose of
enprostil. However, these slight reductions were not augmented significantly by repeated administrations of
enprostil. Slight but significant increase in microsomal
protein content was observed in the group given 14 oral doses of
enprostil and PC.
Enprostil did not affect the other indicators used to evaluate the status of the hepatic
drug metabolizing
enzyme system. Additionally, single or multiple oral doses of
enprostil or PC showed no effect on the
hexobarbital-induced sleeping time. It therefore may be safely concluded that multiple
oral administration, both of
enprostil and of PC, has very little effect on
drug metabolizing
enzyme inducing or inhibiting activity in rats.