89
Fig. 21a), semilogarithmic fitting of the initial data was linear only
up to 100 min. The estimated apparent rate constant was 0.0176 min ^
(half-life = 39 min). This corresponded to the second distributional
half-life (26 min) obtained for buprenorphine from the plasma data
(Table 2). The sigma minus plot of buprenorphine in urine of dog B (Fig.
21b) at 1.6369 mg/kg (Study #2) dose showed curvature, and could be
fitted to a sum of two exponentials. The resulting hybrid rate constants
were 0.026 (half-life = 27 min) and 0.00176 (half-life = 390 min) min
The first half-life corresponded to the second distributional half-life
of buprenorphine (39 min, Table 2) for this dog. For dog C (Fig. 21c) at
1.2023 mg/kg dose (Study #4, Table 2), the sigma minus plot of urinary
data gave an apparent terminal phase rate constant of 0.0017 min ^
(half-life = 400 min). This corresponded with the terminal half-life of
buprenorphine (673 min) obtained from the plasma data. For the same dog
at 1.439 mg/kg dose (Study #5), sigma minus plot (Fig. 21d) showed
curvature, and could be fitted to a sum of two exponentials, and the
respective apparent rate constants were 0.00695 (half-life = 100 min)
and 0.000287 (half-life = 2412 min) min The first half-life obtained
from the urine data corresponded with the second distributional
half-life (61 min, Table 2) obtained for buprenorphine from plasma data.
The sigma minus plots for the urinary excretion of buprenorphine in
other dogs showed great scattering and reasonable estimates of the
apparent rate constants were not possible.
The half-lives obtained from the various sigma minus plots shown in
Fig. 21 for the urinary excretion of buprenorphine reasonably
approximated the first and second distributional half-lives of
buprenorphine in plasma. Since a minor fraction of the the dose was