90
excreted unchanged in urine (<1%) and the limit of detection of
buprenorphine was 5 ng/ml, the terminal half-life of buprenorphine in
dogs could not be readily estimated from the urinary data.
Sigma minus plots for the conjugates (M) are given in Figs. 22,23.
For dog A (Study #1), the curve could be unexpectedly and for no obvious
reason, fitted best by a simple linear equation to indicate a constant
rate of renal elimination even with decreasing plasma concentrations of
the conjugate. The excretion rate was approximately 330 ng/min,
independent of concentration of metabolite in the central compartment
(Fig. 22a). For dog B at 1.6369 mg/kg dose (Study #2) of buprenorphine
(Table 2), the sigma minus plot gave an apparent rate constant of 0.0032
min ^ (half-life = 215 min, Fig. 22b). For dog C at 1.2023 mg/kg dose
(Study #4), (Fig. 22c) an apparent rate constant of 0.0022 min 1
(half-life = 312 min) was obtained, which corresponded well with the
terminal phase half-life obtained for M from plasma data (305 min, Table
2). For dog B at 2.5632 mg/kg dose (Study #3), the sigma minus plot
(Fig. 22d) showed curvature and could be fitted to a sum of two
exponentials, and the apparent rate constants were 0.023 min ^
(half-life = 30 min) and 0.000567 min ^ (half-life = 1220 min)
respectively, where the second half-life corresponded with the terminal
half-life obtained from the plasma data of M in this dog (Table 2,
half-life = 1098 min). The sigma minus plot for M in dog C at 1.439
mg/kg dose (Study #5) showed curvature (Fig. 23) and could be fitted to
a sum of two exponentials, the apparent rate constants being 0.018 min
1 (half-life = 39 min) and 0.000812 min 1 (half-life = 853 min).
In dog C at 1.2023 mg/kg (Study #4) IV bolus dose of buprenorphine,
the terminal half-life of buprenorphine was estimated as 673 min (Table