61
Eq. 12
where is the overall apparent volume of distribution of the
equilibrated fluids of the body.
Thus,
Eq. 13
and
Eq. 14
If 3 or AUC have large errors, then the estimates of have large
errors. Thus the calculated distribution volumes in accordance with
equation 13 based on the best computer fit (Appendix I) of the plasma
data to tri-exponential equation are suspect. However, the calculated
Vj values in accordance with equation 13 (reported in Table 2) averaged
57
434 L, in excess of total body water in dogs (11-15 L) and does
indicate a high degree of sequestration by body tissues.
Dose-independent pharmacokinetics of buprenorphine. The
pharmacokinetic parameters of a drug are dose-independent when all
distribution and elimination processes are first order with respect to
compartmental concentrations. The rate constants must be invariant at
highly varying administered doses and there must be no saturable first
pass metabolism. To establish whether or not there is dose-independency,
the drug is administered to the same animal at different doses. If the
plasma levels divided by the respective doses are superimposable, then
dose independency can be postulated.