English Abstract Eight groups of six male RIV:tox rats received oral and
intravenous doses of benzo(a)pyrene (BaP) in a parallel study plan.
Intravenously and orally four dose levels were administered. BaF was
dissolved in soybean oil for oral administration, and in glycofurol for
intravenous administration. The doses were such, that the absolute oral
bioavailability could be calculated for two dose levels. The plasma
pharmacokinetics of BaP after intravenous administration were described by a
two-compartment model. The corresponding kinetic parameters were
calculated. The elimination half-life of BaP was approx. 30-60 min. in
the period 0-12 h after administration. Therefore, unchanged BaP will not
accumulate after repeated administration, when it is administered once
daily. The AUC values (area under the plasma concentration-time curve)
increased more than proportionally with the oral or intravenous dose. The
deviation from linearity was small for the doses used in this study. After
oral administration multiple plasma concentration maxima were observed,
which may be explained by an interaction of the oil solution with the bile.
The absolute oral bioavailability of unchanged BaP was approx. 13% for a
dose of 1 mg/kg and approx. 4% for a dose of 5 mg/kg. This does not mean,
that the absorption of BaP decreased with increasing doses, because the
non-linear increase of the AUC values with the dose may be explained by
saturation of metabolism. The kinetic parameters and the oral
bioavailability were in the same range as found in the literature for other
rat species.
