a
Values correspond to buprenorphine base. Administered as HC1 salt, dissolved in 30 ml normal saline.
kpf, Af and values equal to P, A and B values expressed in fractions
A and B values were obtained from the nonlinear least square fitting of
of dose per ml of plasma. The P,
54
plasma data with 1/Cp weighting.
C 1
Unit for tt a and 3 values is min Parenthetical values correspond to
cVfean of the weighted residuals. (C = (Q?exp C-Pcapc )/ Q?cagc ). None
statistically significantly different from zero.
half-lives in min.
of the mean residuals were
0 f
' These are the slopes and intercepts of plots of 6 against log fitted cPca]c The parenthetical values
correspond to standard errors. Both slope and intercept were also not significantly different from zero,
indicating that the sum of three exponentials best fits the plasma data of buprenorphine and the conjugate.
^Ratio of the dose to the total area under the plasma concentration-time curve of buprenorphine, where the
calculated AUC = (P/tr ) + (A/a ) + (B/ 0 ) and that calculated from the trapezoidal rule (plus the quotient of
the last observed plasma level Cp(n) and 3) viere within 5-7% in all cases except in dog C at 1.439 mg/kg dose
level where the difference was 10%. Unit, ml/min.
^Estimates from the slopes of cumulative amounts of buprenorphine excreted ( zU ugs) renally against the area
under the plasma concentration time curve (AUC^) at that time in accordance with z U = Cl^^ AUC^
These values were calculated from the initial slopes observed (Figs. 26-28), and these ratios changed as pH of
the urine changed (Fig. 26). The values in parenthesis are ^U at AUC=0 from the best linear plots of data as
shown in Figs. 26-28. The plots of Au/At vs Cp^-md. (Plasma concentration at the mid point of urine
collection interval) were highly scattered in most studies (Fig. 37, see also text).
1C1 was calculated from the difference between total clearance Cl. and renal clearance, Cl of
met tot ren
buprenorphine.
^Cl^et Clg >M was calculated using equation 35.
k 1 1>M
Biliary clearance of M was calculated from the knowledge of Clme^ and (Cl t C1B ) values.
1 M
Renal clearance of metabolite, Clrgn was estimated in accordance with equation 30 (Figs. 32-34).