163
plasma data in studies 10 and 11 were more widely scattered (Figs. 42,
43) than in studies 7, 8, 9 and 12 (Figs. 39-41,44). The terminal
half-lives estimated from the semilogarithmic plots of the terminal
plasma concentrations of buprenorphine against time (and their 95%
confidence limits in parenthesis) were 3938 (3000-5727) and 3357
(2352-5860) min respectively in dogs F and G (see also Table 6). The
estimated averaged first and second distributional half-lives were 29 +_
19 (SEM) min (studies 10, 11 and 12) and 129 _+ 39 (SEM) min (studies
7-12, see Table 5).
The values of k21 and k^, the respective exit rate constants
from the shallow and deep compartments were calculated from the
expressions'
53
k31 = 0.5 [
k21 = 0.5 [
-b-V(b2 4c)]
-b+ V(b2 4c) ]
where
b = ( tt B+ ir A+ 3 P+8 A+ a p+ a B) / (P+A+B)
and
Eq. 46
Eq. 47
Eq. 48
Eq. 49
c = (otir b+t: 8 A+a 8 P)/(P+A+B)
where P, A and B values were obtained from equations 16-18.
For a drug conforming to a 3-compartment body model, the equation
that describes the time course of the drug in the central compartment
. 53
is
CP,
calc
(k0/Vc) C[ (k21 w ) (k3l -7r ) (l-e* T) /" ( a it ) ( tt 8 ) ]
[(k21 -a)(k31 -a)(l-ea T)/a(7r-a)(a-8)] eat +
[(k21 8) (k31 -6 ) (1-e 5T )/ B(o-B) (8 -ir )] e"3 t ] Eq. 50
vhere T is the duration of infusion and t is the time after initiating
-w t