165
where
Q = (k0/VJ [ (k21-TT ) (k31- TT ) / IT ( a -TT )(*-(? )]
R = (k0/vc) t(k21-ct ) (k31-a ) / a (it a) (a 3) ]
Eq. 53
Eq. 54
and
S = (k0/Vc)[(k2r3)(k3re ) / 3 (-3 ) ( 3-tt ) ]
Eq. 55
The post-infusion area 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),
AUCoo = (P'/11 ) + (A7a) + (B'/e )
Eq. 56
Thus, AUC = AUCfl^ + AUC' and the calculated areas are given
OO v i oo
in Table 5.
The total clearances, Cltot, calculated from the equation Cl^^
= Dose/AUC^ were 246, 201 and 239 ml/min (see also Table 5) for dogs
F, G and H respectively. The average total body clearance estimated for
all 6 dogs was 211 +_ 13.7 (SEM) ml/min (Table 5 and 6). The 95%
confidence limits for these clearances are reported in Table 6. This
value is lower than the total clearance obtained from IV bolus studies
(396 +_ 19 (SEM) ml/min, Table 2). Thus over estimation of Clt t value
in IV bolus studies could be attributed to the lack of sufficient number
of quantifiable terminal plasma points to obtain reasonable estimates of
terminal rate constant, and the derived total body clearance. The
overall volume of distribution V^ estimated from the equation 13 was
616 +_ 52 (SEM, n=6) L, indicating high degree of sequestration into body
tissues, consistent with the observations from IV bolus studies (434 L,
Table 2).
Plasma pharmacokinetics of the derived metabolite (M). The
brachialis and jugular vein plasma concentrations of buprenorphine