240
f
a
= Adf, ,,
1(oral)
xf /
AUC^
1(IV)
.oral
O
Eq. 64
Thus the calculated percentages of the dose absorbed were 10 and 20
respectively in dogs B and D (Study #15,16, Table 8), and the fractions
of the doses cleared by first-pass metabolism before reaching the
systemic circulation, estimated in accordance with the equation
f. = 1 (f/f ) Eq. 65
pm a' ^
were 40 and 82% respectively in dog B and D (Study #15,16). The extent
of first pass metabolism estimated from the ratios of the total body
clearance and hepatic blood flow (360-400 ml/min in a 20-kg dog^)
were 0.6 and 0.43 in dogs B and D. This contradiction may be explained
by one or more of the above assumptions not being valid. Studies with
37 38
rat gut preparations have demonstrated gut wall metabolism of
buprenorphine. Thus any significant gut wall metabolism would
overestimate the first-pass metabolism calculated in accordance with
equation 65.