95
2). The plasm data and sigma minus plot of M in this dog gave an
apparent terminal half-lives of 305 (Fig. 18) and 312 (Fig 22c)
respectively. This metabolite half-life is therefore, an apparent
distributional half-life and not the terminal half-life.
Urinary excretion rate plots. Since xc = vc Cp in equation 19,
substituting the value of Cp from equation 2 into equation 19,
Tvi-ii Tt ^ ,iii -at niii -8 t
dU/dt =P e + A e +B e
where P111 = P k V
u c
.in , T7
A = A k V
u c
B111 = B k V
u c
Eq. 24
Eq. 25
Eq. 26
Eq. 27
A semilogarithmic plot of excretion rate of unmetabolized drug
versus time according to equation 24 would yield a triexponential curve.
As with the semilogarithmic plasm concentration-time plot, the terminal
exponential phase rate constant can be obtained from the terminal slope,
- 3/2.303, and B111 is the extrapolated intercept of the terminal
linear phase to time zero. Similar to the treatment of the plasm data
with multicompartment characteristics, the method of residuals could be
used to obtain the parameters of the distributional phases of equation
24.
Semilogarithmic plots of A U/ At (approximations of the
instantaneous excretory rate, dU/dt), finite amounts (A U) of either 1
or M excreted during a finite time interval ( a t) against t-mid
(mid-point of the collection interval) were highly scattered in most of
the studies. Thus only the data for dog A (Study #1) and B (Study #2)
are reported here. In dog A (Study #1), urine data of buprenorphine up