162
Thus, the total area is
AUC^ = AUCq_t (during infusion) + AUC^ (post-infusion) Eq. 45
These calculated areas are given in Table 5.
The total clearances, CltQ^, calculated from the equation
Cltot = Dose/AUC^ were estimated as 213, 152 and 213 ml/min in dogs
B, D and E respectively (Table 5 and 6). The 95% confidence limits for
these clearances are reported in Table 6. The overall volumes of
distribution estimated from the equation 13 were 595, 443 and 561 L
respectively in dogs B, D and E, indicating high degree of sequestration
of buprenorphine into body tissues.
Three compartment model. In slow IV infusion studies 10, 11 and 12,
the post-infusion plasma concentrations of buprenorphine as a function
of time were fitted to a sum of three exponentials in accordance with
54
the equation 15 using the computer program of Yamaoka et. al.
(Appendix I, Figs. 42-44). The plasma concentrations were weighted by
their inverse values. The validity of the triexponential equation 15 was
confirmed by demonstration that regressions of the weighted residuals
(calculated in accordance with the equation 3) against logarithm of the
calculated buprenorphine plasma concentrations gave mean residuals £,
slopes and intercepts which were not statistically significantly
different from zero (Fig. 48, Table 5).
The parameters of the above sum of three exponential fits of the
post-infusion plasma data of buprenorphine are listed in Table 5 in
addition to the calculated parameters (equations 15-18) for an
equivalent IV bolus administration. The estimated terminal half-lives of
buprenorphine in the body were 5195, 5254 and 2337 min respectively in
dogs F, G and H (studies 10, 11 and 12 respectively). The terminal