Læknablaðið : fylgirit - 01.05.1978, Side 73

mean4 SE:
t -test :
Wilcoxon :
ANOVAR :
Friedman :
Figu re 4.
meam SE :
t -test :
Wilcoxon :
ANOVAR :
Friedman :
Figure 5.
1.2
1.1
1<H
.9
.8
.7
.6
.5
.44
hr
.1
-0.586
'21
-0.744
0 500 mg-2
0.66640.092 0.738 í 0.066
decreased the serum conoentrations by 30%, a
statistically highly significant decrease. The
large dose of aspirin did not alter the serum
concentration of indomethacin, however.
From fig. 4 it can be seen that k2i is
unaffected by concurrent administration of aspirin.
This also applies for the elimination rate constant
. (fig. 5). Vj however did increase in consequence
of treatment with aspirin. The increase observed
. in case of the low dose of aspirin was statisti-
cally significant judged by students' t-test (fig.6).
. Fig. 7 illustrates that the total plasma clearance
—• 0.596 calculated as the product of Vi and ke was
J increased by 1/3 in consequence of treatment with
aspirin in a low dose. This increase was stati-
stically significant judged by various tests.
*_____ In agreement with this finding fig. 8 shows
1000mg-2 that the area under the serum concentration-
time curve decreased by almost 1/3 in conse-
0.605í 0.071 quence of treatment with aspirin.
1.6'
1.5
1.4
1.3
1.2
-6-1.177
1.1' •
1.1*740.091
NS
NS
NS
NS
•<e
I
Ns Discussion:
(gg The mechanism behind the demonstrated kinetic
interaction between aspirin and indomethacin
remains unexplained. It has been established
that aspirin in vitro displaces indomethacin from
its binding to albumin, presumably by causing
structural changes of the albumin molecule.9 As
we are measuring the sum of protein bound and
free indomethacin, a displacement from protein
binding may account for the decreased serum
concentrations and hence the increased apparent
volume of distribution in the central compartment.
However, this cannot possibly be the entire
explanation since the serum concentration of indo-
methacin decreased only when a low dose of
. aspirin was administered.
In our opinion the most likely explanation is
** that it is not the aspirin that displaces indo-
methacin from the protein binding sites, but a
normal constituent of human serum, the concen-
tration of which being affected by aspirin. Uric
—•—1.014 acid may possibly be this constituent as its
• concentration in serum increases with low doses
. of aspirin and decreases with large doses.
------,-----------------*------
500 mg ■ 2 1000 mg-2
1.19840.064 1.078 4 0.098
NS NS
NS NS
NS
NS
C onclusion:
It has beendemonstratedthat aspirin may
decrease the serum concentration of indomethacin
by increasing the apparent volume of distribution
in the central compartment and the total plasma
clearance. Until the clinical significance of this
pharmakokinetic interaction has been established
a concurrent administration of indomethacin and
aspirin should be avoided.
71