PHARMACOKINETICS OF THE IV ADMINISTERED METABOLITE
Semilogarithmic plots of plasma concentrations of the metabolite
against time after 7 and 8.5 min constant rate infusion of the
metabolite in studies 13 and 14 in dogs F and G respectively are shown
in Figures 72,73 (Table 7). Dog G was bile cannulated and the bile was
collected up to 22 h in this dog (Study #14).
The post-infusion plasma concentrations of the metabolite were
fitted to a sum of three exponentials in accordance with equation 15
54
using the computer program of Yamaoka et. al. (Appendix I). 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 the logarithm of the estimated
concentrations of the metabolite gave mean residuals C, slopes and
intercepts which were not statistically significantly different from
zero (Fig. 74, Table 7).
The parameters of the sum of three exponentials that best fit the
post-infusion plasma data of buprenorphine are listed in Table 7. In
addition, the calculated parameters (equations 15-18) for an equivalent
IV bolus administration are given. The terminal half-lives of the IV
administered metabolite were 392 and 319 min respectively in dogs F and
G (Studies 13,14). The estimated average terminal half-life of the
metabolite in plasma following IV administration of the parent drug was
1846 min (Table 2). The fact that terminal half-life of the IV
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