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The Interaction of thiol drugs and urine pH in the treatment of cystinuria.
[cystinuria]
Pharmacological
therapy
for
cystinuria
consists
of
alkali
salts
to
increase
urine
pH
and
thiol
drugs
to
form
soluble
cysteine-drug
complexes
.
The
effect
of
alkalinizing
urine
on
thiol
drug
activity
has
not
been
well
studied
.
Urine
samples
were
obtained
from
5
healthy
subjects
and
pH
was
adjusted
(
range
6
.
0
to
8
.
0
)
in
each
urine
aliquot
.
Urine
samples
were
incubated
with
cystine
crystals
at
37
C
for
5
,
15
and
60
minutes
,
and
48
hours
.
We
compared
cystine
solubility
in
urine
samples
spiked
with
thiol
drugs
at
a
final
concentration
of
2
mM
to
that
in
control
urine
samples
at
the
various
pH
levels
and
time
points
.
In
samples
incubated
for
48
hours
,
which
is
the
standard
time
frame
for
solubility
studies
,
cystine
solubility
more
than
doubled
with
thiol
drugs
compared
to
control
and
did
not
depend
on
pH
.
However
,
when
incubation
time
was
shortened
to
5
minutes
,
representing
the
dwell
time
of
urine
in
the
renal
pelvis
,
the
effect
of
thiol
drugs
to
solubilize
cystine
greatly
depended
on
urine
pH
with
less
cystine
dissolved
at
lower
pH
.
Increasing
urine
pH
greatly
increased
the
efficacy
of
thiol
drugs
to
solubilize
cystine
in
a
clinically
relevant
time
frame
.
These
findings
suggest
that
to
maximize
the
benefit
of
thiol
drugs
alkali
therapy
should
be
used
in
conjunction
with
thiol
drugs
with
the
goal
of
keeping
urine
pH
at
7
.
5
or
above
.
Clinical
trials
are
needed
to
confirm
these
in
vitro
findings
.
Diseases
Validation
Diseases presenting
"the effect of thiol drugs to solubilize cystine greatly depended on urine ph with less cystine dissolved at lower ph"
symptom
cystinuria
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