Læknablaðið : fylgirit - 01.05.1978, Page 72

physiological entities. For example is the term
ke used to denote the rate of the overall elimina-
tion, i.e. the sum of the rates for biotrans-
formation in the liver, renal filtration and
excretion etc.
If ia drug is administered instantaneously to
the central compartment a plot of the natural
logorithm as a funetion of the time after the
administration gives a curve with two distinct
linear components; the initial called the alpha
or the distribution phase and the second slower
phase the beta or the elimination phase. The
final slope is inversely proportional to the bio-
logical half-life, but not equal to -ke (eq.2).
A computer programme was written which
through an iterative process converted the four
parameters o<,^i , k^i and Vi in order to reduce
the sum of squared differences between the experi-
mentally determined concentration-time data and
the values calculated from Eq. 1. From these
four parameters ke, kj2 and V2 were calculated
according to Eqs. 2, 3 and 4, respectively. The
area under the concentration-time curve from the
time of administration to any time "t" was calcu-
lated by integration (Eq. 5).
In order to evaluate the statistical significance
of the parameter estimates the computer pro-
gramme included a calculation of their asymptotic
standard deviations. If the standard deviation
exceeded half the parameter value, the parameter
estimate was considered to be too unreliable and
was excluded form the rest of the analysis.
B es ults:
Fig. 2 shows a typical semilogarithmic plot of
the serum concentration as a function of the time
for one person. The line indicates the concen-
trations predicted by the two-compartmental
model. It can be scen that for 5 hours the
model renders a good description of the data.
Six hours after the administration however,
there is a rise in the serum concentration for .
this and all the other persons. The reason for
this secondary rise in the serum concentration
has not been established, but a reasonable
explanation might be that indomethacin excretcd
in the bile is being reabsorbed from the gut.
Whatever the reason may be, thc phenomenon
restricted the kinetic analysis to the first 5 hours.
Fig. 3 shows a linear plot of thc mcan serum
concentration for all persons before and after
treatment with aspirin. It can be seen that
aspirin 500 mg twice daily during 1 week
70