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Dear subscribers,
I have the task of attempting to calculate what one's alcohol level might be
given one clinical test, either breath or blood determination in combination
with the individuals recounting of the evening's consumption. This "back
calculation" is frought with difficulties, assuming population averages for
each of these individual circumstances.
Frequently, the tale told by the individual seems not to coincide with the
determination method used clinically. It is then my duty to reconcile this
information and issue and opinion. Often, it is easy to assume, given an
individuals alcohol influenced state that his recollection is probably
errored. However, there are often other circumstances that may account for
the apparent discrepancies.
What I am asking for is three-fold:
What medications (as complete a list as possible) lead to delayed gastric
emptying that would affect the rate of absorbtion;
What medications induce increased metabolism, or compete for metabolism
(since alcohol is predominantly zero order kinetics) ;
Is there a method of determining one's individual metabolic rate of alcohol
that might be employed that could reliably determine and account for one's
individual deviation from the general population averages.
Specific references would be appreciated if at all possible, or any help at
all.
Sincerely,
J. Daniel Fleming B.S. Pharm.
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[A few replies - db]
X-Sender: mentor.aaa.hardlink.com
Date: Wed, 21 Jul 1999 00:45:57 -0400
To: PharmPK.aaa.boomer.org
From: Daro Gross
Subject: Re: PharmPK Re: alcohol CY induction
This is not my area of specialty, but I stumbled on an interesting
discovery that might be of assistance. Electrical conductivity of
high-voltage (low amp) current through a muscle appears to be directly
related to a person's metabolism and speed of metabolizing alcohol. I do
not have a good explanation since it was a discovered by chance, but you
might look into it and get back to me. I'd like to know if this can be
shown to be an effective measurement over a general population in a
controlled study.
---
Sender: gmould.-a-.dial.pipex.com
Date: Wed, 21 Jul 1999 10:59:58 +0100
From: Graham Mould
To: PharmPK.-at-.boomer.org
Subject: Alcohol CY induction
To Daniel
I have been involved from a legal point of view with some of these
alcohol back extrapolation problems in the UK with drivers who have been
stopped by the police and may have consumed too much alcohol. So far I
have worked on "population" data from a single breath alcohol
concentration or blood concentation and the courts have accepted my
calculations. I think you are right in that the patients view of events
are somewhat tainted either by the fact that they might lose their car
license or a genuine hangover. The former is probably more the case. As
you know, very little affects the metabolism of alcohol and the only
major factor I consider affecting absorption is the presence of food.
see Lewis (1986) Journal of the Forensic Science Society 26 95-113.
Graham Mould
Guildford Clinical Pharmacology Unit
Royal Surrey County Hospital
Phone: 00 44 1483 406886
Fax: 00 44 1483 455375
---
X-Sender: shoaf.aaa.clinpharm.niaaa.nih.gov (Unverified)
Date: Wed, 21 Jul 1999 11:19:07 -0400
To: PharmPK.aaa.boomer.org
From: shoaf.-a-.clinpharm.niaaa.nih.gov
Subject: Re: PharmPK Re: alcohol CY induction
None of this really has to do with CYP2E1 induction but here goes
>I have the task of attempting to calculate what one's alcohol level might be
>given one clinical test, either breath or blood determination in combination
>with the individuals recounting of the evening's consumption. This "back
>calculation" is frought with difficulties, assuming population averages for
>each of these individual circumstances.
>Frequently, the tale told by the individual seems not to coincide with the
>determination method used clinically. It is then my duty to reconcile this
>information and issue and opinion. Often, it is easy to assume, given an
>individuals alcohol influenced state that his recollection is probably
>errored. However, there are often other circumstances that may account for
>the apparent discrepancies.
Have you seen References:
Guidelines for estimating the amount of alcohol consumed from a single
measurement of blood alcohol concentration: re-evaluation of Widmark's
equation.
AUTHORS: Gullberg RG; Jones AW
AUTHOR AFFILIATION: Washington State Patrol, Seattle 98102.
SOURCE: Forensic Sci Int 1994 Dec 1;69(2):119-30
Estimation of the amount of alcohol ingested from a single blood alcohol
concentration.
AUTHORS: Wagner JG; Wilkinson PK; Ganes DA
SOURCE: Alcohol Alcohol 1990;25(4):379-84
Ethanol kinetics: extent of error in back extrapolation procedures [see
comments]
AUTHORS: al-Lanqawi Y; Moreland TA; McEwen J; Halliday F; Durnin CJ;
Stevenson IH
AUTHOR AFFILIATION: Department of Pharmacology and Clinical Pharmacology,
University of Dundee,Ninewells Hospital and Medical School, Dundee.
SOURCE: Br J Clin Pharmacol 1992 Oct;34(4):316-21
Comment in: Br J Clin Pharmacol 1993 Jun;35(6):669-70
Backtracking booze with Bayes--the retrospective interpretation of blood
alcohol
data. (see Figure 1 its a scream!)
AUTHORS: Jackson PR; Tucker GT; Woods HF
AUTHOR AFFILIATION: University Department of Medicine and Pharmacology,
Royal Hallamshire Hospital,Sheffield.
SOURCE: Br J Clin Pharmacol 1991 Jan;31(1):55-63
>What I am asking for is three-fold:
>What medications (as complete a list as possible) lead to delayed gastric
>emptying that would affect the rate of absorbtion;
High doses of Ethanol are well absorbed from the stomach so delay of
gastric emptying of empty stomach is not really a major factor. Ranitidine
and Cimetidine are reported to affect low doses of alcohol but these are
not the people you are concerned with. Consumption of ethanol with food
(after food) will alter Cmax and tmax. See "Food effects on absorption and
metabolism of alcohol."
AUTHORS: Sedman AJ; Wilkinson PK; Sakmar E; Weidler DJ; Wagner JG
SOURCE: J Stud Alcohol 1976 Sep;37(9):1197-214
>What medications induce increased metabolism, or compete for metabolism
>(since alcohol is predominantly zero order kinetics) ;
The fact that it is zero order kinetics is irrelevant. Anything that is an
inhibitor of the alcohol dehydrogenase enzyme will slow ethanol
elimination. None are prescribed that I can think of (pyrazole,
methylpyrazole, etc.). No medications have been shown to enhance ethanol
metabolism. Metabolism has been reported to be higher in chronic (as
opposed to binge)alcoholics but not individuals that consume moderate
amounts of ethanol daily.
>Is there a method of determining one's individual metabolic rate of alcohol
>that might be employed that could reliably determine and account for one's
>individual deviation from the general population averages.
Yes, follow decline of breath alcohol concentrations following
administration of alcohol in a standardized protocol.
>Specific references would be appreciated if at all possible, or any help at
>all.
>
>Sincerely,
>J. Daniel Fleming B.S. Pharm.---
Regards,
Susan Shoaf, Ph.D.
Acting Chief
Unit of Pharmacokinetic Studies
NIAAA/LCS
shoaf.-at-.clinpharm.niaaa.nih.gov
10 Center Dr., MSC-1256
301-496-4936
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Daniel:
Sorry for not getting back earlier - vacations you know
I have been dealing both clinical and legal issues related to alcohol now fo=
r
over two decades. (In my previous life I was the Lab Dir. in a speciality
institution where we had an inpatient alcohol and drug treatment program). Y=
ou
are correct back extrapolation is froth with problems but you can put window=
s
i.e the projection is from x mg/100ml to y mg/100ml. Thats the way I have de=
alt
with this in many court cases.
Be aware that when you do calculations that variable such as age, gender,
height and weight are included. Age is an important variables in males and i=
s
generally ignored in the various formulas I have seen. Some formulas even do
not account for gender differences!!!
(A paper I published details the variables that effect BAC: B. Kapur: CBAC:
Computerized Blood Alcohol Concentration - A Computer Model as a Clinical an=
d
an Educational Tool, Ann. Biochim. Clin. Qu=E9. 30(2):36-39 (1991)).
You may also find the following paper interesting:
F. Curtis Breslin, Bhushan M. Kapur, Mark Sobel and Howard Cappell: Gender=
and
Alcohol dosing: A Procedure for Producing Comparable Breath Alcohol Curves f=
or
Men and Women, Alcohol Clin Exp Res, 21(5): 928-930, (1997
>What medications (as complete a list as possible) lead to delayed gastric
>emptying that would affect the rate of absorbtion;
There are no drugs that I am aware of that will effect gastric emptying at
lease not when large volumes of alcohol is consumed as is the case with your
patients.
>Is there a method of determining one's individual metabolic rate of alcohol
>that might be employed that could reliably determine and account for one's
>individual deviation from the general population averages.
Serial sampling is the only way I know off to determine the individual
metabolic rate. Although literature suggests metabolic rates to be any wher=
e
from 10mg/100ml to 25mg/100ml per hour, in the patients I have followed the
average is about 18mg/100ml/hr. Heavy drinkers generally are between
20mg/100ml/hr and 25mg/100mL/hr. The highest I have seen in an alcoholic is
36mg/100ml/hr.
>What medications induce increased metabolism, or compete for metabolism
4-methyl pyrazole is the only drug I know which competes with alcohol
dehydrogenase. Recent study (NEJM April 1999 - sorry do not have the title a=
t
hand) has shown 4-MP's usefulness in treating ethylene glycol poisoning. (EG=
is
also metabolized by ADH). 4-MP is not used as a drug for any other purpose t=
hat
I am aware of.
bhushan
------------
Dr. Bhushan M. Kapur, D.Phil, C.Chem, FRSC, FACB, FCACB
b.kapur.-a-.utoronto.ca; bkapur.at.sickkids.on.ca
Consultant in Toxicology
Assistant Professor of Clinical Biochemistry
Department of Laboratory Medicine and Pathobiology
Faculty of Medicine, University of Toronto
&
Division of Clinical Pharmacology and Toxicology
The Hospital for Sick Children
Toronto, ON M5G 1X8
homepage: http://www.clinitox.com
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Dear all:
Re: drug effects on alcohol absorption rates
Drugs which might reduce the rate of absorption of alcohol and therefore
Cmax and AUC via delayed gastric emptying could include: A)the opiates
such as codeine taken for headaches as it is metabolised to morphine
which has been shown to reduce gastric emptying of liquids ( see Murphy
DB et al 1997 Anesthesiology 87 765-770) and B) levodopa. (see
Robertson DRC 1990, British J Clin Pharmacol, 29, 47-53). Erythromycin
and the prokinetics, such as metoclopramide, domperidone and cisapride,
might well have the opposite effect.
Andrew Sutton
Andrew Sutton
ASutton.-a-.gcpl.co.uk
Guildford Clinical Pharmacology
Innovators in Phase 1 model design
and leaders in Phase 2 recruiting.
Telephone +44 (0) 1483 406886
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