164
infusion in min. During infusion, T=t and upon cessation of infusion, T
becomes a constant equal to the time of infusion. In the above
expression, except for V all the other constants are known. Thus it
is possible to obtain Vc the volume of distribution of the central
compartment by fitting the post-infusion data with the above equation
with one unknown parameter. Curve fittings of the infusion data to the
54
above equation using the computer program of Yamaoka et al. (Appendix
I) are given in Figs. 41-43 (See also Table 5). The apparent volumes of
distribution of the central compartment (VJ estimated by this
procedure were 35.4, 69.6 and 5.3 L respectively for dogs F, G and H.
Vc was also calculated from equation 10 where the values of the
parameters P, A and B (Table 5) were obtained through equation 16-18.
The estimated apparent volumes of distribution of the central
compartment by this procedure were 35.3, 69.1 and 5.3 L respectively in
dogs F, G and H, which are in agreement with the above Vc values
calculated by the computer fitting of the post-infusion data to equation
50.
Estimation of AUC for plasma buprenorphine. When the constants in
equation 41 are simplified into single constants, the following equation
results during infusion:
Cp = Q (e 7Tt -1) + R (e_a 1 -1) + S (e3 1 -1) Eq. 51
Integrating the above expression between 0 to T, the time infusion was
ended, gives:
AUCq_t = (Q / 7T ) (1-e" 1 t) + (R / a ) (l-e_a t) +
- Bt
(S / 6) (1-e
t)
Eq. 52