0
The mean and standard error of mean were computed for dogs B, D, E and G only. The mean SEM for dog F and G
were significantly different fran the other four dogs. However, the terminal plasma data on these two dogs had
greater scattering (See Figs. 42,43) then the dogs B, D, E and G.
^ Af, B^ and values were calculated from the A, B and C values obtained from equations 16-18 and
expressed as fractions of the total dose Xq per ml of plasma.
^ The theoretical area under the plasma concentration-time curve of buprenorphine during the infusion phase
was calculated using equation 41 in dogs B, D and E. In dogs F, G and H, equation 52 was used.
Post-infusion area under the plasma concentration-time curve was obtained by integrating equation 15 between
T to oo, AUC^,^ = (P'/ ir) + (A'/ ) + (B'/ 8 ) .
1 The total area under the plasma concentration-time curve was calculated using the trapezoidal rule. This
area was used in the estimation of total body clearance and apparent volume of distribution of buprenorphine
(V.) in dogs.
-* In study #10, the calculated area by trapezoidal rule up to 1616 min was 260508 ng.min/ml. The quotient of
the plasma concentration of buprenorphine (38.2 ng/ml) at at 1616 min and the average terminal phase rate
constant (0.000345/min) was 105234 ng.min/ml. Thus the total area was estimated as 371233 ng.min/ml.
Mean of the weighted residuals calculated in accordance with the equation 3. None of the mean residuals were
statistically significantly different iron zero.
1 m
' Slopes and intercepts of the plots of C against log fitted post-infusion data. The parenthetical values
correspond to standard errors. Both slopes and intercepts were not statistically significantly different from
zero, indicative of the fact that in dogs B, D and E, the sum of two exponentials and in dogs F and G, the sum
of three exponentials best fit the post-infusion plasma data of buprenorphine.
n Ratio of the infused total dose to the total area under the plasma concentration-time carve of
buprenorphine. The AUC^ was calculated using trapeziodal rule. The calculated total clearances in studies
7-12 were 203, 128, 225, 152, 194, 244 ml/min respectively which averaged 191 + 18 (SEM) ml/min.
Estimates iron the slopes of the cumulative amounts of buprenorphine excreted ( EU, pg) renally against the
area under the plasma concentration-time curve of buprenorphine in accordance with the equation 30. These
ratios changed as pH of the urine changed. (See Fig. 57). Values given in parenthesis correspond to EU at
AUC=0 from the best linear plots of the data shown in Figs. 57,58.
^ Clj^e^M was calculated using equation 58.
^ C1M the renal clearance of the plasma metabolite was calculated in accordance with the equation 30,
see afso Fig. 59.
154