236
wall metabolism and no saturable first-pass metabolism
Eq. 62
Since total body clearance is the same irrespective of the route of
administration, equations 61 and 62 can be equated and on rearrangement,
the fraction of the dose that eventually reaches the systemic
circulation is
.oral
X AUCr*
0 oo
f = (1-f. ) f = -T-
lpm a Yoral
0
Eq. 63
.IV
oo
Plots of the plasma concentration-time profile of buprenorphine and
conjugate are presented in Fig. 81 for dog B and D following 84.7 and
87.11 mg oral doses of buprenorphine respectively. In dogs B and D
(Study #15,16), the apparent bioavailability f of buprenorphine
estimated in accordance with equation 63 (Table 8) were 6 and 3.7%
respectively.
If the following assumptions are valid, i.e., a) the drug is
eliminated from the body virtually completely by hepatic metabolism, b)
there is no gut wall metabolism, c) there is no saturable first-pass
metabolism, d) when the drug is delivered to the liver through either
portal vein or hepatic artery, the extent of first-pass metabolism is
the same, and e) a constant fraction of the hepatically derived
metabolite reaches the systemic circulation, then the areas under the
plasma concentration-time curves of the metabolite obtained after oral,
AUC^(ral)' 311(1 IV administration, AUC^, of the parent
compound can be compared to estimate the fraction of the dose absrobed
unchanged: