Transcript Time Breath alcohol concentration (mg/l)

Clinical Pharmacokinetics of
Alcohol in A CDAT Sample
Robert Cohen
Consultant Addiction Psychiatrist
9.11.2012
Introduction
• The way the body
handles alcohol is of
interest to a number
of different groups
• Back calculation of
alcohol is based on the
assumption that the
body clears 1 unit of
alcohol per hour (zero
order kinetics)
• Zero order kinetics – same
rate of removal however
much alcohol left
• First order kinetics – the
more alcohol in the blood
stream, the quicker it is
removed
• Limited use of alcohol
testing in the clinical
setting
• Result of testing often
limited to positive or
negative
– Though the readings
in blood, breath and
hair are quantitative
and need
interpretation
Alcohol testing
• Ethanol (ethyl alcohol)
or metabolites can be
tested in a variety of
matrices
–
–
–
–
–
Blood
Breath
Sweat
Urine
Hair
• Breath alcohol levels
closely parallel arterial
blood levels
Jones & Andersson, For Sci Int
2003;132: 18
The breathalyser
• Presents an easy
method to test for
alcohol levels
• Easy to carry out the
test
• Reliable machinery
This study
Kingston
CDAT
LDASS
The problem of interpreting
breathalyser readings
• When you take a breathalyser reading, you
do not know
– When the person last drank
– How much they drank
• But you may be able to gain an
understanding if you know the rate of
elimination,
– which you can work out by taking multiple
readings
• This study is a pilot into the start of this
question
Methods
• 20 consecutive patients who attended for
assessment for alcohol / drug problems
and whose breathalyser reading was more
than 0.00mg/l
• Breath alcohol level readings taken at
regular intervals
• Rate of elimination calculated and
compared to the concentration
• A composite made of all the readings
Time
14:12
Breath alcohol
concentration
(mg/l)
1.69
Time
14:12
14:27
Breath alcohol
concentration
(mg/l)
1.69
1.55
Time
14:12
14:27
Breath alcohol
concentration
(mg/l)
1.69
1.55
Rate of
Elimination
(mg/l/hr)
0.56
Time
14:12
14:27
14.42
Breath alcohol
concentration
(mg/l)
1.69
1.55
1.47
Rate of
Elimination
(mg/l/hr)
0.56
0.32
Time
50
13
:
30
13
:
15
13
:
00
13
:
30
12
:
00
12
:
40
11
:
25
11
:
10
11
:
55
10
:
40
10
:
25
10
:
Breath EtOH conc (mg/l)
2.5
2
1.5
1
0.5
0
Time
50
13
:
30
13
:
15
13
:
00
13
:
30
12
:
00
distribution
12
:
40
11
:
25
11
:
10
11
:
55
10
:
40
absorption
10
:
25
10
:
Breath EtOH conc (mg/l)
2.5
clearance
2
1.5
1
0.5
0
Results
• 20 patients at the time of audit
• 10 patients used only alcohol (‘alcoholics’)
• 10 patients used alcohol on top of
methadone (‘drug addicts’)
• All met the criteria for a clinical ICD-10
diagnosis of mental and behavioural
disorder due to use of alcohol, dependent
type (F10.2)
Results - Demographics
Alcoholics
Drug Addicts
N
Male
10
5 (50%)
10
8 (80%)
Age – mean (range)
Weekly units of
alcohol – mean
(range)
50 (38-68)
133.6 (0-284)
35.9 (26-44)
202.3 (56-455)
Results – Breathalyser Readings
N
Total # of readings
Alcoholics
Drug Addicts
10
32
10
44
Range of number of 2-6
readings per patient
Readings (mg/l)
0.04-1.05
Range - reduction
-0.04-0.58
rate (mg/l/hour)
2-13
R for reduction rate
& alcohol
concentration
0.43 (p=0.003)
0.46 (p=0.007)
0.03-2.00
-0.68-1.88
All patients
Alcoholics
Drug Addicts
Discussion - findings
• Alcohol clearance in people with the
alcohol dependence syndrome appears to
follow first order kinetics rather than zero
order kinetics
– This is a composite picture of 20 patients,
rather than a full study of individuals over the
whole of the pharmacokinetic profile
(absorption, distribution and clearance)
– This is therefore a pilot study, generating a
hypothesis for formal testing
Discussion – clinical implications
• Potential to lead to biologically based
diagnosis of alcohol dependence
• Biological support for drinking reduction as
a therapeutic step prior to detoxification
• Possible clinical-biological difference
between those only using alcohol and
alcohol/opiate users
Discussion – clinical implications-1
• If there are clinical differences in the
pharmacokinetics of alcohol between
dependent people and non-dependent
people, this may form the basis of a
clinical biologically based test for alcohol
use disorder, as opposed to history / rating
scale based diagnosis
• This is for future investigation
Discussion – clinical implications-2
• This work may eventually elucidate the
plasma level of alcohol associated with
onset of withdrawal symptoms
• However, clinical observations of patients
with low plasma levels (e.g., 0.10mg/l) is
mixed
– Some show withdrawal symptoms
– Others do not
Discussion – clinical implications-2
• If withdrawal symptoms
drive alcohol consumption
in dependent patients then
more rapid clearance may
be lead to greater
consumption, thereby
creating a vicious circle
• Helping people reduce
consumption rather than
attain immediate abstinence
may therefore be an
appropriate clinical goal as
a step prior to detoxification
Higher
alcohol
level
Greater
need to
drink
Faster
alcohol
clearance
Plasma
reduction
felt more
Discussion – clinical implications-3
• There may be a difference between those
who are in addition opiate dependent and
those who are only dependent on alcohol
– There is some evidence for this (Clarke, JSAT
2006; 30:191)
• But the findings in this study may also be
attributable to the higher level of drinking
by opiate dependent patients
Thank you for listening
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