59
The parameters of the above equation were obtained by fitting the
buprenorphine plasma data of dogs 1-6 to equation 2 using the computer
54
program of Yamaoka et. al. (Appendix I). The values of the parameters
of equation 9 are given in the legends of Figs. 4-9 or can be calculated
from the normalized values given in Table 2. The calculated percent
contribution of the term B/3 of the terminal area to the total area in
studies 1-6 were 72, 68, 53, 44, 58 and 47 respectively. This
demonstrates the significance of 3 in the estimation of AUC^ and
consequently the total body clearance derived from this value (Equation
8). Thus, uncertainties in the estimates of 6 can lead to uncertainties
in the estimates of AUC and total body clearance. In the IV bolus
oo
studies (#1-6), the contributions of the terms P/ir and A/a were only
about half of the total area under the plasma concentration time curve.
When equation 2 was used to fit the plasma data of buprenorphine
54
(Yamaoka et. al., Appendix I), the P, ir A, anda parameters were
estimated from the data in high range (50-5000 ng/ml) of plasma
concentrations. These data are held in greater confidence than the
estimates obtained from the low values of the terminal phase. Thus, if
the error in AUC estimation is primarily due to the error in the
oo
estimation of 6 the 95% confidence limits for AUC and the derived
oo
total body clearance (Equation 8) can be estimated from the terminal
rate constant, 3 and its standard error.
To estimate the error in AUCqq (Equation 9), the parameters P, tt ,
A, anda were obtained by fitting the complete plasma data of
buprenorphine to the tri-exponential equation 2 (using the computer
54
program of Yamaoka et. al. Appendix I). However, the parameters B
and 3 were obtained from the regressions of the semilogarithmic plots of