161
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. 39-41 (See also Table 5). The apparent volumes of
distribution of the central compartment (V ) estimated by this
procedure were 31, 19.6, and 47.1 L respectively (Table 5). Vc was also
calculated from equation 10 where the values of the parameters A and B
(dose-normalized, shown in Table 5) were obtained through equations
17,18. The estimated apparent volumes of distribution of the central
compartment by this procedure were 31, 19.5, and 47.1 L respectively
which agreed with the above Vc values estimated by the computer fitting
of the post-infusion plasma data to equation 39.
Estimation of AUC. When the constants in equation 39 are simplified
into single constants, the following equation results during infusion:
Cp = R (e_ott -1) + S (e-Bt -1) Eq. 40
Integrating the above expression between 0 to T, the time infusion was
ended, gives:
AUC0_t = (R/d ) (l-e"at t) + (S/e ) (1-e" t) Eq. 41
where
R = (k0/VJ [ (k21-a ) / a (a B ) ] Eq. 42
and
S = (k0/Vc) [ (k21-e )/ 3(3-01)] Eq. 43
The post-infusion area (AUC^) under the plasma
concentration-time curve was obtained by integrating the equation 15
between (t-T)=0, the time when infusion was stopped, to time infinity
(oo),
AUCo = (A'/a ) + (BV 3)
Eq. 44