Urine pentamidine as an indicator of lung pentamidine in patients receiving aerosol therapy


Smaldone, G.C.; Vinciguerra, C.; Morra, L.

Chest 100(5): 1219-1223

1991


To determine if urine pentamidine was reflective of lung pentamidine, we compared levels of the drug in bronchoalveolar lavage fluid and simultaneously obtained urine. Thirty-one patients who were receiving aerosolized pentamidine either as treatment or as prophylaxis underwent BAL and submitted urine samples for pentamidine analysis. Pentamidine was analyzed in both phases of BAL fluid (supernatant and cell pellet) and in urine using high performance liquid chromatography. Urine results were normalized for creatinine. Patients were categorized as prophylaxis failures (active Pneumocystis carinii pneumonia on prophylaxis), electives (free from PCP on prophylaxis), treatment (daily AP in treatment doses for active PCP, or miscellaneous (single dose of AP). Levels in BAL fluid and urine varied widely over several orders of magnitude. However, for all patients, we found a highly significant relationship between BAL supernatant and urine (r=0.97, p<0.0001). No statistical differences were found when comparing levels of pentamidine between failures and electives; however, the number of failures was small. We conclude that urine pentamidine is related to lung pentamidine and can be used as a clinical indicator in patients receiving aerosolized therapy.

Urine
Pentamidine
as
an
Indicator
of
Lung
Pentamidine
in
Patients
Receiving
Aerosol
Therapy*
Gerald
C.
Smaldone,
M.D.,
Ph.D.;
Colleen
Vinciguerra,
R.N.,
M.S.;
and
Lorraine
Morra,
B.S.
To
determine
if
urine
pentamidine
was
reflective
of
lung
pentamidine,
we
compared
levels
of
the
drug
in
broncho-
alveolar
lavage
fl
uid
and
simultaneously
obtained
urine.
Thirty-one
patients
who
were
receiving
aerosolized
pentamidine
either
as
treatment
or
as
prophylaxis
under-
went
BAL
and
submitted
urine
samples
for
pentamidine
analysis.
Pentamidine
was
analyzed
in
both
phases
of
BAL
fl
uid
(supernatant
and
cell
pellet)
and
in
urine
using
high
performance
liquid
chromatography.
Urine
results
were
normalized
for
creatinine.
Patients
were
categorized
as
prophylaxis
failures
(active
Pneumocystis
carinii
pneumonia
on
prophylaxis),
electives
(free
from
PCP
on
prophylaxis),
treatment
(daily
AP
in
treatment
doses
for
active
PCP,
or
miscellaneous
(single
dose
of
AP).
Levels
in
BAL
fluid
and
A
erosolized
pentamidine
is
widely
used
to
prevent
PCP
in
patients
infected
with
the
human
immu-
nodeficiency
virus.
The
AP
reduces
PCP
-relapse
rates
by
50
percent
and
delays
recurrence
by
six
months.'
Although
it
has
not
been
approved
for
treatment
in
active
infection,
some
studies
have
revealed
promising
results
when
used
for
mild
PCP.
2
.
3
The
pharmacokinetics
of
AP
are
not
thoroughly
understood.
Studies
have
shown
significant
variability
in
pentamidine
delivery
to
the
lung
with
nebulizer
selection
and
particle
size
being
critical
factors.'•
5
Following
aerosol
therapy,
bronchoalveolar
concentra-
tions
are
substantially
greater
than
those
attained
after
intravenous
pentamidine
while
plasma
concentrations
are
minimal.
6
The
pulmonary
half-life
has
been
shown
to
be
prolonged
following
aerosol
administration
with
pentamidine
detectable
in
BAL
fl
uid
for
up
to
115
days
following
two
weeks
of
daily
consecutive
treat-
ment.
6
Elimination
of
the
drug
occurs virtually
unal-
tered
via
the
kidney
when
given
intravenously
and
trace
amounts
have
been
detectable
in
the
urine
following
inhalation."
Despite
its
success,
prophylaxis
failure
in
patients
using
AP
is
a
concern.
A
failure
rate
of
13
percent
has
been
reported
using
the
approved
regimen,
300
mg
*From
the
Department
of
Medicine,
Pulmonary/Critical
Care
Division,
State
University
of
New
York
at
Stony
Brook,
Stony
Brook,
NY.
This
study
was
supported
by
the
AIDS
Clinical
Trials
Group
Al
25893
from
the
National
Institutes
of
Health
Manuscript
received
February 1;
revision
accepted
March
26.
Reprint
requests:
Dr.
Smaldone,
Pulmonary
Disease
Division,
SUNY,
HSC
T-17-040,
Stony
Brook,
New
York
11794-8172
urine
varied
widely
over
several
orders
of
magnitude.
However,
for
all
patients,
we
found
a
highly
significant
relationship
between
BAL
supernatant
and
urine
(r
=0.97,
p<0.0001).
No
statistical
differences
were
found
when
comparing
levels
of
pentamidine
between
failures
and
electives;
however,
the
number
of
failures
was
small.
We
conclude
that
urine
pentamidine
is
related
to
lung
pentam-
idine
and
can
be
used
as
a
clinical
indicator
in
patients
receiving
aerosolized
therapy.
(Chest
1991;
100:1219-23).
AP=
aerosolized
pentamidine;
HPL,C=
high
performance
liq-
uid
chromatography
via
nebulizer
(Respirgard
II)
on
a
monthly
basis."
The
same
study
determined
that
patients
receiving
second-
ary
prophylaxis
(prior
episode
of
PCP)
were
at
greater
risk
for
failure
than
those
receiving
primary
prophy-
laxis
(no
history
of
PCP).
However,
predictability
of
prophylaxis
failure
for
the
individual
patient
has
not
been
established.
In
the
present
paper,
we
performed
BAL
in
HIV
-
infected
individuals
receiving
AP
who
clinically
rep-
resented
the
entire
spectrum
of
pulmonary
involve-
ment
with
PCP.
Using
HPLC,
pentamidine
levels
were
determined
in
lavage
fl
uid
and
simultaneously
obtained
urine.
We
reasoned
that,
in
patients
receiving
aerosolized
pentamidine
therapy,
the
lung
burden
of
pentamidine
closely
reflects
the
total
body
stores.
If
so,
this
burden
may
be
a
determinant
of
daily
urinary
excretion.
We
found
a
close
correlation
between
lung
lavage
fl
uid
levels
of
pentamidine
and
urinary
levels.
This
observation
suggests
that
urinary
pentamidine
may
be
useful
in
assessing
adequacy
of
therapy,
patient
compliance,
and
caregiver
exposure.
MATERIALS
AND
METHODS
Patient
Selection
Four
groups
were
studied
as
follows:
aerosol
pentamidine
pro-
phylaxis
and
new
onset
of
PCP
(failures);
patients
with
active
PCP
who
received
three
weeks
of
daily
aerosolized
pentamidine
treat-
ment
(treatment);
aerosol
pentamidine
prophylaxis
and
free
from
PCP
(electives);
and
patients
who
had
received
only
one
dose
of
aerosol
prophylaxis
(miscellaneous).
In
general,
patients
in
the
failure
group
received
their
last
dose
of
AP
within
four
weeks
of
BAL.
The
treatment
group
underwent
BAL
within
24
h
following
CHEST
/
100
/
5
/
NOVEMBER,
1991
1219
21
days
of
therapy
with
600
mg
via
nebulizer.
For
the
elective
group,
the
last
dose
of
prophylaxis
was
administered
between
two
days
and
six
weeks
prior
to
BAL;
this
wide
range
allowed
for
analysis
between
peaks
and
troughs.
In
the
two
miscellaneous
patients,
BAL
was
performed
33
and
18
days
after
a
single
dose
of
AP
Informed
consent
for
both
the
BAL
and
urine
sampling
was
obtained
on
all
patients.
Patients
were
excluded
from
the
study
if
they
were
currently
undergoing
treatment
with
intravenous
pentamidine.
Five
patients
had
received
treatment
with
intravenous
pentamidine
5
to
12
months
prior
to
the
study.
Nocedure
All
patients
underwent
BAL
either
as
a
diagnostic
or
elective
procedure.
The
bronchoscope
was
introduced
in
a
standard
manner,
and
following
an
endobronchial
exam,
was
wedged
into
the
medial
segment
of
the
middle
lobe,
unless
medical
circumstances
dictated
that
the
lavage
be
done
in
another
area.
The
BAL
fl
uid
was
collected
into
three
separate
suction
traps.
The
initial
trap
was
utilized
to
collect
any
residual
lung
fl
uids
from
the
lung
examination;
the
remaining
two
traps
were
used
for
collection
of
lavage
fl
uid.
Lavage
was
performed
using
a
total
of
300
ml
of
normal
saline
solution
given
in
60
ml,
60
ml,
and
30
ml
aliquots
per
trap.
Midway
through
the
lavage,
the
trap
was
changed.
A
typical
total
output
yielded
approximately
130
to
150
ml.
The
initial
trap
was
sent
to
microbi-
ology
for
routine
cultures
when
required.
The
remaining
traps
were
utilized
for
cytologic
assessment
for
PCP
and
pentamidine
analysis.
Raw
fl
uid
was
subdivided
into
aliquots
of
5
ml
from
each
trap
and
centrifuged
for
10
min
at
1500g.
The
supernatant
was
decanted;
both
supernatant
and
cell
pellets
were
frozen
at
—29°C
until
analysis.
This
method
served
to
standardize
volume
while
providing
a
supply
of
samples
for
reproducibility
checks.
Reported
results
represented
the
average
of
four
determinations,
two
from
each
trap.
Previous
studies
on
BAL
fl
uid
have
indicated
minimal
dilution
Table
1
—Patient
Characteristics
Age/Sex
Primary
vs
Secondary
Prophylaxis
History
Last
Dose
Prior
to
BAL,
Days
Time,
mo
Dose,
mg
Freq
Nebulizer
Failure
1*
43/M
Secondary
8
60
2
x
/Month
Pulmosonic
9
2
39/M
Secondary
4
300
Monthly
Respirgard
II
24
3
51/M
Secondary
11
75
2
x
/Month
Aerotech
II
Unknown
4
35/M
Secondary
12
300
Monthly
Respirgard
II
21
5
37/M
Primary
18
120
2
x
/Month
Pulmosonic
7
Mean
SD)
41
(±6.3)
10.6
(±5.2)
Treatment
6
39/M
None
<1
7
41/M
None
<1
8*
43/M
Secondary
6
60
2
x
/Month
Pulmosonic
<1
9
29/M
None
<1
Mean
(±SD)
38
(±6.2)
Elective
10
41/M
Secondary
4
300
Monthly
Respirgard
II
6
11
46/M
Secondary
7
300
Monthly
Respirgard
II
21§
12
30/F
Primary
9
75
2
x
/Month
Aerotech
II
18§
13
25/M
Primary
7
300
Monthly
Respirgard
II
20*
14
42/M
Secondary
7
300
Monthly
Respirgard
H
11
15
58/M
Secondary
9
300
Monthly
Respirgard
II
33*
16
40/M
Secondary
21
75
2
x
/Month
Aerotech
lit
16
17
29/F
Primary
7
300
Monthly
Respirgard
II
28*
18*
31/M
Secondary
3
150
Monthly
Aerotech
II
22§
19
40/M
Primary
6
300
Monthly
Respirgard
II
2*
20
46/F
Secondary
6
300
Monthly
Respirgard
H
2#
21
35/M
Primary
6
300
Monthly
Respirgard
II
2*
22
53/M
Primary
12
300
Monthly
Respirgard
II
28§
23
42/M
Secondary
4
300
Monthly
Respirgard
II
28§
24
25/M
Primary
2
300
Monthly
Respirgard
H
at
25*
28/M
Secondary
5
300
Monthly
Respirgard
II
3*
26
33/M
Primary
6
300
Monthly
Respirgard
II
16
27
29/M
Primary
6
300
Monthly
Respirgard
II
13
28
38/F
Primary
14
300
Monthly
Respirgard
II
18§
29*
31/M
Secondary
10
300
Monthly
Respirgard
H
42
Mean
(
±
SD)
37
(
±
9.1)
7.6
(±4.3)
Miscellaneous
30
33/M
Primary
1
300
Monthly
Respirgard
II
33
31
44/F
Primary
1
300
Monthly
Respirgard
II
18
Mean
(
SD)
39
(
±
7.8)
*Received
intravenous
pentamidine
between
5
and
12
months
prior
to
study.
tFirst
18
months
of
treatment
with
Pulmosonic,
60
mg
2
x
/month.
*Designated
peak.
*Designated
trough.
1220
Urine
Pentamidine
as
Indicator
of
Lung
Pentamidine
(Sanaicione,
Vinciguerra,
Marra)
effects
from
the
patient's
own
body
fl
uid
in
serial
traps
obtained
from
our
lavage
procedure.'
Urine
samples
were
collected
from
each
patient
the
same
day
the
BAL
was
performed.
Approximately
15
ml
of
random
urine
was
collected
in
polypropylene
containers;
1
ml
was
set
aside
for
creatinine
analysis
to
correct
for
differences
in
daily
free
water
excretion.
The
remaining
urine
was
stored
at
-
29°C
until
analysis.
Results
from
duplicate
samples
were
averaged.
The
BAL
samples
(supernatant
and
cells)
and
urine
were
analyzed
for
pentamidine
using
HPLC.
A
specific
assay,
adapted
by
Conte
et
al"
was
applied
to
each
specimen,
and
results
were
reported
(ng/ml)
for
BAL
supernatant
and
cell
pellet
and
nanograms
of
pentamidine/
milligrams
creatinine/milliliter
for
urine.
Standard
curves
were
spiked
with
known
amounts
of
pentamidine
isethionate
to
serve
as
an
external
standard
in
a
range
to
accommodate
expected
values.
Hexamidine
isethionate
(200
ng)
was
added
as
the
internal
standard
regardless
of
sample
type
or
range.
Statistical
Analysis
Data
were
organized
demographically
to
compare
groups.
Pen-
tamidine
levels
in
BAL
fl
uids
(supernatant
and
cell
pellet)
were
related
to
each
other
and
to
urine
levels
using
simple
regression
and
Student's
t
-test.
RESULTS
A
total
of
31
patients
were
studied
in
all
groups:
5
failures,
20
electives,
4
treatment,
and
2
miscellaneous.
Patient
characteristics
by
grouping
with
regard
to
age,
sex,
and
pentamidine
history
are
summarized
in
Table
1.
The
groups
were
well
matched
with
regard
to
age.
Twenty-six
(84
percent)
patients
were
men
and
fi
ve
(16
percent)
were
women.
Twenty-eight
(90
percent)
patients
were
receiving
AP
as
prophylaxis;
three
patients
in
the
treatment
group
were
not
receiving
prophylaxis
prior
to
active
PCP
Prophylaxis
history
ranged
from
1
to
21
months
with
a
mean
of
7.6
±
4.7
(SD)
months
for
all
patients
(10.6
±
5.2
months
for
failures;
7.6
±
4.3
months
for
electives).
The
one
patient
in
the
treatment
group
who
was
receiving
prophylaxis
was
taking
it
for
six
months.
In
the
miscellaneous
group,
both
patients
received
their
one
dose
of
AP
as
primary
prophylaxis;
one
of
these
patients
was
found
to
be
positive
for
PCP
at
the
time
of
this
study.
The
BAL
and
urine
pentamidine
results
are
sum-
marized
in
Table
2.
Levels
of
pentamidine
were
detected
in
patients
who
had
as
little
as
one
prophy-
lactic
dose
(the
miscellaneous
group).
Both
BAL
and
urine
pentamidine
levels
were
greatest
in
patients
receiving
treatment
with
AP
for
21
days.
Those
levels
averaged
fi
ve
to
ten
times
those
from
patients
receiving
prophylaxis.
There
was
no
statistical
difference
be-
tween
mean
pentamidine
levels
of
patients
in
the
failure
group
when
compared
to
those
in
the
elective
group.
In
the
elective
group,
pentamidine
levels
were
further
analyzed
according
to
the
day
of
the
last
dose
(ie,
peak
vs
trough).
For
the
peak
levels,
BAL
was
performed
within
three
days
of
the
last
dose;
for
the
troughs,
BAL
was
performed
approximately
three
to
four
weeks
after
the
last
dose.
In
general,
the
mean
peak
levels
were
higher
than
the
mean
trough
levels
for
BAL
and
urine;
however,
these
differences
were
not
statistically
significant.
Relationships
between
BAL
fl
uids
and
urine
sam-
ples
are
li
sted
in
Table
3.
With
all
four
groups
combined,
there
was
a
highly
significant
relationship
(r
=0.97,
p<0.0001)
between
BAL
supernatant
and
urine
(Fig
1).
Other
relationships
of
interest
included
those
between
supernatant
and
cell
pellet,
cell
pellet
and
urine,
and
the
total
of
both
BAL
phases
(super-
natant
and
cell
pellet)
and
urine
which
all
appeared
significant
(Table
3).
However,
levels
in
all
fl
uids
for
the
treatment
group
and
one
additional
patient
(10)
in
the
elective
group
far
exceeded
all
other
values,
and
it
was
possible
that
the
indicated
regression
coeffi-
cients
reflected
differences
between
these
groups
Table
2
-Summary
of
BAL
(ng/ml)
and
Urine
Pentamidine
(ng/mg
Creatinine/ml)
Levels
by
Patient
Group
Supernatant
Cell
Pellet
Total
BAL
Fluids
Urine
Failure
(n
=5)
Range
5.7
to
55.7
25.3
to
296.3
31.0
to
352.0
25.7
to
76.6
Mean
SD)
22.5
(
±-
19.3)
96.3
113.2)
118.7
(
±
131.9)
43.1
20.3)
Treatment
(n
=
4)
Range
179.0
to
251.6
209.3
to
870.5
445.9
to
1049.5
406.4
to
777.9
Mean
SD)
222.3
(±31.3)
610.4
282.8)
832.7
(
±
267.5)
635.5
164.0)
Elective
(n
=
20)
All
patients
Range
2.0
to
74.8
14.9
to
1122.1
26.2
to
1197.0
1.3
to
246.8
Mean
(±.-
SD)
20.5
(
±
16.9)
122.1
240.8)
142.6
(±254.3)
62.3
(±64.0)
Peak
(n=
5)
Mean
SD)
27.6
(
±
14.7)
95.0
77)
122.5
(±86.3)
87.2
(
±
70.1)
Trough
(n
=
9)
Mean
SD)
13.9
(±6.1)
56.0
(±42.3)
69.9
45.2)
42.5
(±36.9)
Miscellaneous
(n
=2)
Range
10.3
to
34.6
20.5
to
78.6
30.9
to
113.2
9.8
to
79.4
Mean
SD)
22.4
(±17.1)
49.6
41.1)
72.0
(
±
58.2)
44.6
(±49.2)
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Table
3
—Relationships
Between
BAL
Fluids
and
Urine
(n=31)
r
Value
p
Value
Supernatant
vs
cell
pellet
All
patients
0.69
<0.0001
Patients
6,7,8,9,
10
excluded
0.62
<0.0001
Cell
pellet
vs
urine
All
patients
0.67
<0.0001
Patients
6,7,8,9,
10
excluded
0.09
NS
Supernatant
+
cell
pellet
vs
urine
All
patients
0.77
<0.0001
Patients
6,7,8,9,
10
excluded
0.17
NS
Supernatant
vs
urine
All
patients
0.97
<0.0001
Patients
6,7,8,9,
10
excluded
0.50
0.009
rather
than
a
true
correlation
between
individual
values.
Therefore,
all
regressions
were
retested
with
the
treatment
group
and
patient
10
removed.
All
correlations
remained
significant
except
those
involv-
ing
the
cell
pellet
and
urine.
The
fi
ve
patients
who
had
received
intravenous
pentamidine
within
one
year
of
participating
in
this
study
were
highlighted
in
the
fi
gure
to
assess
for
potential
long-term
effects
from
pentamidine
seques-
tered
in
other
organs.
Their
data
are
uniformly
scat
-
800
0
0
0
r
-
0.97,
p
<
0.0001
0
100
200
300
BAL
supernatant
(ng/ml)
FIGURE
1.
Relationship
between
urine
and
BAL
supernatant
pen-
tamidine
levels
for
all
patients
(y=
—3.1231
+
2.8771x,
r
=
0.97,
p<0.0001).
Closed
circles
represent
patients
who
received
intrave-
nous
therapy
within
5
to
12
months
prior
to
BAL.
tered
among
the
group
suggesting
little
effect.
DISCUSSION
This
study
analyzed
pentamidine
levels
in
BAL
fl
uid
and
urine
of
patients
who
were
receiving
AP
over
a
wide
range
of
doses
including
daily
treatment
and
monthly
prophylaxis.
Among
those
receiving
prophy-
laxis,
fi
ve
different
dosing
regimens
had
been
used
with
three
different
nebulizers.
Patients
who
were
prophylaxis
failures
and
the
treatment
group
were
actively
infected
with
Pneumocystis
while
the
elective
individuals
were
clinically
well.
Despite
the
variability
in
therapeutic
regimens
and
pulmonary
involvement,
we
found
a
strong
correlation
in
all
subjects
between
BAL
supernatant
and
urine
levels
(r
=0.97,
p<0.0001).
Within
a
patient
group,
variation
in
BAL
pentami-
dine
may
reflect
many
variables,
for
example,
amount
of
pentamidine
actually
deposited,
timing
of
bron-
choscopy,
pulmonary
inflammation,
etc.
However, all
groups
were
clustered
about
the
same
relationship
for
BAL
supernatant
vs
urine
regardless
of
clinical
con-
dition,
dose,
or
time
of
study.
The
correlation
with
"spot"
urines,
corrected
for
creatinine,
suggests
that
pentamidine
in
lung
supernatant
is
continuously
ex-
creted
at
a
constant
rate
via
the
blood
into
the
urine.
The
cell
pellet
may
represent
a
storage
phase
in
equilibrium
with
the
supernatant.
This
path
is
sup-
ported
by
the
correlation
between
BAL
supernatant
and
cell
pellet
and
the
lack
of
a
significant
relationship
between
cell
pellet
and
urine
levels.
Our
data
were
not
supportive
of
differences
between
failure
levels
and
levels
in
the
elective
(potentially
protected)
group.
However,
the
number
of
failures
studied
was
small,
and
therefore,
no
general
statement
can
be
made
to
support
or
negate
this
relationship.
Additionally,
in
the
elective
group,
no
statistically
significant
relationship
could
be
found
when
separat-
ing
this
group
into
peaks
and
troughs.
Again,
these
numbers
were
small.
In
spite
of
the
small
numbers,
the
wide
range
in
values
seen
in
each
group
indicates
that
urine
testing
is
sensitive,
and
as
shown
by
one
miscellaneous
patient,
can
provide
levels
four
weeks
after
a
single
dose.
These
data
suggest
that
urine
pentamidine
levels
may
be
used
as
an
indicator
of
pentamidine
in
the
lung
for
those
on
AP
who
have
not
had
recent
treatment
with
intravenous
pentamidine
(ie,
within
six
months).
These
fi
ndings
have
potential
clinical
implications.
For
example,
this
test
can
be
used
as
a
measure
of
patient
compliance.
Nebulizer
delivery
is
complex
and
often
requires
direct
supervision.
For
patients
who
are
not
observed
or
who
are
treated
at
home,
urine
levels
can
provide
an
estimate
of
penta-
midine
delivery.
In
addition,
this
tool
can
be
important
in
assessing
1222
Urine
Pentamidine
as
Indicator
of
Lung
Pentamidine
(Smaldone,
Vinciguerra,
Morra)
the
lung
burden
of
pentamidine
in
clinical
studies
of
drug
efficacy.
Our
present
understanding
of
prophy-
laxis
failure
is
incomplete.
Clinical
studies
have
sug-
gested
that
relapse
is
related
to
regional
inhomoge-
neity
of
pentamidine
deposition
in
the
lung
possibly
due
to
regional
differences
in
ventilation.
9
However,
regional
pentamidine
levels
and
regional
ventilation
have
not
been
related
to
failure.
Further,
in
a
recent
study,
we
found
no
correlation
between
regional
ventilation
and
regional
pentamidine
deposition
in
patients
treated
with
nebulizers
(Respirgard
II
and
Aerotech
11).
4
If
failure
is
due
to
inadequate
delivery
(even
to
parts
of
the
lung),
the
total
lung
burden
may
be
different
in
these
subjects
when
compared
to
the
population
of
protected
patients.
Other
factors,
such
as
lung
clearance
and
organism
resistance,
may
be
important.
Our
study
shows
that
urine
testing
provides
similar
data
to
direct
sampling
via
bronchoscopy
and
may
be
useful
in
analyzing
mechanisms
of
failure
in
prophylaxis
and
treatment
with
AP
Data
from
the
present
study,
however,
are
insufficient
to
answer
this
question.
Finally,
urine
pentamidine
testing
may
provide
an
index
of
inadvertent
exposure.
Environmental
control
regarding
AP
is
an
issue
of
concern
to
both
health
care
agencies
and
to
those
who
deliver
the
drug.
In
health
care
workers,
virtually
all
exposure
can
be
expected
to
be
via
the
inhaled
route.
The
long
half-
life
of
pentamidine
in
the
lung
precludes
accurate
estimates
of
total
burden
via
intermittent
air
sampling.
Urine
samples,
however,
reflect
the
lung
burden,
and
serial
samples
should
represent
the
cumulative
expo-
sure
over
time
to
the
caregiver
population.
Additional
studies
are
needed
to
determine
if
urine
pentamichne
analysis,
using
HPLC,
will
be
useful
in
assessing
mechanisms
of
prophylaxis
failure
and
caregiver
ex-
posure.
ACKNOWLEDGMENTS:
The
authors
thank
Drs
John
E.
Conte
Jr.,
Emil
T.
Lin,
and
their
technical
staff
for
their
consultative
assistance
in
the
development
of
our
HPLC
technique.
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JA,
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D,
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H,
Feigal
D,
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JE.
Prevention
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Lancet
1989;
1:654-
57
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AB,
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JM,
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J,
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RJ,
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KJ,
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