58
infinity? Fig. 4, top inset). This large range for the confidence limits
is attributable to the estimation of a terminal rate constant from few
(n=3) plasma values. The estimated terminal rate constants from the
semilogarithmic plots of the terminal plasma cocentrations against time,
their respective standard errors, and 95% confidence limits are given in
Table 3.
The terminal half-life estimated for studies 1,2,4,5 and 6 have
relatively less error compared to study 3 (Table 3). Yet, estimation of
the true terminal half-life depends on the number of terminal plasma
values, the time interval between these values and the number of
terminal half-lives over which the samples were collected. The terminal
plasma data in studies 1,2,4,5, and 6 were not representative of the
true terminal phase since the plasma data needed to accurately estimate
the terminal half-life were below the analytical sensitivity and were
not available.
Total body clearance. The total body clearance Cl^t of a dose,
53
XQ, can be calculated from
Cl
tot
- VAUCoo
Eq. 8
where AUC^ = area under the plasma concentration-time curve up to time
infinity. AUCt up to the last observed plasma point, Cp^ can be
calculated by the trapezoidal rule. The area from the last plasma
sampling time to infinity can be estimated from Cpn / 8 where g is the
terminal rate constant. Also, AUC^ can be explicitly calculated by
integrating equation 2 between time 0 to oo, i.e.,
AUC^ = (P/tt ) + (A/a ) + (B/0 )
Eq. 9