220
Table 7. Continued . .
a Dose in mg corrospond to buprenorphine conjugate assayed by acid
hydrolysis followed by HPLC separation and fluorimetric detection.
Time of infusion in min.
Q
P'f, A'^, and B'^ are the intercepts obtained by fitting the
post-infusion plasma data to equation 15 by nonlinear least square curve
fitting using the computer program of Yamaoka et al. (Appendix I) where
plasma concentrations were weighted by their inverse values. The
intercepts are expressed as fractions of the total dose per ml of
plasma.
^ Unit for tt a and 3 values is min Parenthetical values corrospond
to half-lives in min.
Pfr Aand values were calculated using equations 16-18 and
expressed as fractions of the total dose per ml of plasma.
The theoretical area under the plasma concentration-time curve of
buprenorphine during the infusion phase was calculated lasing equation
52.
^ Post-infusion area under the plasma concentration-time curve was
obtained by integrating equation 15 between T to oo, AUC- =
(P'/ir ) + (A1 / a ) + (B'/ 3). 1-00
Mean of the weighted residuals calculated in accordance with the
equation 3. None of the mean residuals were statistically significantly
different from zero.
1,-) Slopes and intercepts of the plots of 6 against log fitted
post-infusion data. The parenthetical values corrospond to standard
errors. Both slopes and intercepts were not statistically significantly
different from zero, indicating that the sum of three exponentials best
fits the post-infusion plasma data of buprenorphine conjugate.
Ratio of the infused total dose to the total area under the plasma
concentration-time curve of buprenorphine conjugate. The AUC was
calculated from equations 52 and 56. The values in parenthesis
correspond to 95% confidence limits.
1 Estimates from the initial slopes of the cumulative amounts of
buprenorphine conjugate excreted ( £U, yg) renally against the area
under the plasma concentration-time curve of the conjugate in accordance
with the equation 30. Values in parenthesis corrospond to at AUC=0
from the best linear plots of the data shown in Figs. 77,78.
m Clg was calculated from a plot of the cumulative amount of the
conjugate excreted in bile against the area under the plasma
concentration time profile of the conjugate.