60
the terminal phase plasma data against time. The standard error value,
sm, of the terminal slope was multiplied by the t-value (obtained from
t table for a=0.025 level of significance, two tailed for (n-2) degree
of freedom; where n is the number of terminal plasma points). The
resulting g+_ t.sm permitted the estimation of the the upper and lower
95% confidence limits for AUC calculated in accordance with equation
oo
9. The upper and lower limits for the CltQt were derived from the upper
and lower limits of AUC in accordance with equation 8. These calculated
total body clearances and the respective 95% confidence limits are
reported in Table 3 for the 6 TV bolus studies in the dogs.
Volumes of distribution of buprenorphine. The plasma concentration
53
of a drug in the central compartment at time zero is given by
CpQ = P+A+B = XQ / V, Eq. 10
when an IV bolus is administered into a 3-compartment body model. Vc is
the apparent volume of distribution of the central compartment. The
average Vc was 13.1 +_ 2.73 (SEM) L (Table 2). This value exceeds the
56 57
volume of blood (1.8 L) and the extracellular water (4.8-6.6 L) in
dogs. This indicates rapid sequestration of the drug in the
extracellular space upon bolus administration.
If the clearing organ is in the central compartment (Scheme II),
53
then the clearance from the central compartment, Clc, is given by
Cl = V k.n Eq. 11
c c 10 ^
If the drug is solely eliminated from the body through the central
compartment, the Clc is the total body clearance Cltot at any time
53
during the post-distributive phase in accordance with the equation,