156
accordance with the equation 3) against logarithm of the calculated
plasma concentrations gave mean residuals , slopes and intercepts which
were not statistically significantly different from zero (Fig. 48, Table
5).
The parameters of the above sum of biexponential fits of the
post-infusion plasma data of buprenorphine are listed in Table 5 in
addition to the calculated parameters (equations 17,18) for an
equivalent IV bolus administration. The estimated average terminal
half-lives of buprenorphine were 1934, 2019, and 1824 min in dogs B, D
and E respectively. The estimated 95% confidence limits for the terminal
rate constants are given in Table 6.
The value of the exit rate constant from the deep
. 53
compartment was calculated from the expression
k21 = (A 8 +Ba ) / (A+B) Eq. 38
where A and B were obtained from equations 17,18.
For a drug conforming to a 2-compartment body model, the equation
that describes the time course of the drug in the central compartment
(k0/Vc) [ [ (k21 -a) (l-eaT)/a(ct-8)] e~at
+ [(8-k21)(l-e pT )/ 8 (a -8 )] e" 3t ] Eq. 39
where T is the duration of infusion and t is the time after initiating
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 Vc, all the other constants are known. Thus it
is possible to obtain V,, the volume of distribution of the central
compartment by fitting the post-infusion data with the above equation