Alcohol toxins. H. Stanbro
The Doctors
How long do toxins from alchohol remain in the liver and urine? For
how many hours after a drink (or multiple drinks) is consumed
are these
toxins detectable?
Answer
I'm not quite sure what "toxins" you are thinking of.
Ethanol is
metabolized into acetaldehyde and other substances a certain
amount of
which are found in the body anyway. Most tests for alcohol intoxication
look for ethanol itself in the breath, blood or urine. There is some
individual variation in the rate at which ethanol is
metabolized, and of
course a lot depends on what form it was ingested in, whether
food or
other drinks were taken at the same time, whether the person has chronic
liver or kidney disease which might affect the rate of
metabolism, the
person's body weight and body composition (how much of the
weight is
bone, fat, body water), time of day, etc. Here are a couple of
publications examining the variation in alcohol metabolism in normal
subjects:
Clin Pharmacokinet 1987 Nov;13(5):273-92
Clinical pharmacokinetics of ethanol.
Holford NH
Department of Pharmacology and Clinical
Pharmacology, School of Medicine, University of Auckland.
The pharmacokinetics of ethanol after typical
doses are described by a 1-compartment model with
concentration-dependent
elimination. The volume of distribution
estimated from blood concentrations is about 37 L/70 kg.
Protein binding of ethanol has not
been reported. Elimination is
principally by
metabolism in the liver with small amounts excreted in the
breath (0.7%), urine (0.3%), and
sweat (0.1%). Metabolism occurs, principally
by alcohol dehydrogenase, in the liver to acetaldehyde.
Models of ethanol input and
absorption are crucial to the
description and
understanding of the effects of ethanol dose on bioavailability.
Little attention has been
paid to evaluation of potential models.
First-pass extraction of ethanol is predicted to be
dependent on
hepatic blood flow and ethanol
absorption rate, with a typical
extraction ratio
of 0.2. The overall elimination process can be described by a
capacity-limited model
similar to the Michaelis-Menten model for
enzyme kinetics. The maximum rate of elimination of ethanol
(elimination capacity or Vmax
is 8.5 g/h/70 kg. This would be
equivalent to a
blood ethanol disappearance rate of 230 mg/L/h if metabolism
took place at its
maximum rate. The elimination rate is
half of
the elimination capacity at a peripheral blood ethanol
concentration (Km) of about 80
mg/L. Ethanol is readily detectable
in expired
air. The usual blood:expired air ratio is 2300:1 and breath
clearance at rest is 0.16 L/h.
The renal clearance of ethanol is
0.06 L/h and
sweat clearance is 0.02 L/h. The use of a zero-order model of
ethanol elimination has
been widespread although the
limitations of
this model have been known for a long time. Much of the
published work on ethanol
pharmacokinetics must be regarded with
suspicion because of this assumption.
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Br J Clin Pharmacol 1994 May;37(5):427-31
Between-subject and within-subject variations
in the pharmacokinetics of ethanol.
Jones AW, Jonsson KA
Department of Alcohol Toxicology, University
Hospital, Linkoping, Sweden.
1. Twelve healthy men drank 0.80 g ethanol
kg-1 body weight on four occasions spread over several
weeks. Ethanol was given as
96% v/v solvent which was diluted
with orange
juice to make a cocktail (20-25% v/v). This drink was ingested
in exactly 30 min at
08.00 h after an overnight (10 h)
fast. 2.
Samples of venous blood were obtained at exactly timed
intervals of 0, 10, 20, 30, 45, 60,
90, 120, 150, 180, 240, 300, and 360 min
after the start of drinking. The concentrations of ethanol in
whole blood were determined
by headspace gas chromatography. 3.
Summary measures were used to evaluate the
concentration-time profiles of ethanol for each
subject. The between-subject and
within-subject components of variation for the
pharmacokinetics of ethanol were derived by
one-way analysis of variance (ANOVA). 4.
The variation between different subjects dominated the total
variance for all of the
pharmacokinetic parameters studied
except the
rate of disappearance of ethanol from blood (ko). For this
latter parameter, 42% and
58% of the total variation arose from variations
between- and within-subjects respectively. These results might
be important to
consider when experiments on the clinical
pharmacokinetics of ethanol are being planned.
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Br J Clin Pharmacol 1997 Dec;44(6):521-6
Effect of high-fat, high-protein, and
high-carbohydrate meals on the pharmacokinetics of a small
dose
of ethanol.
Jones AW, Jonsson KA, Kechagias S
Department of Forensic Toxicology, National
Laboratory of Forensic Chemistry, University Hospital,
Linkoping, Sweden.
AIMS: To investigate whether the relative
amounts of fat, carbohydrate (CHO), or protein in a meal
influence the pharmacokinetics of
a small dose of ethanol. METHODS: Nine
healthy men received ethanol (0.30 g kg-1 body weight) on
five occasions in a randomized
cross-over fashion. On three
occasions the
dose of ethanol was consumed within 15 min of eating a
standardized breakfast of similar
volume and calorific value but containing
different amounts of fat, CHO, and protein. On two other
occasions the same dose of ethanol
was ingested on an empty stomach (overnight
fast) or administered by intravenous (i.v.) infusion over 30
min. RESULTS: The
blood-ethanol profiles showed large
inter and
intraindividual variations, especially when ethanol was
ingested after eating food. The
peak blood-alcohol concentrations
(BAC) were
16.6 +/- 4.0, 17.7 +/- 7.1, and 13.3 +/- 4.0 mg dl-1 (mean +/-
s.d.) after fat, CHO,
and protein-rich meals and 30.8 +/-
4.3 and
54.3 +/- 6.4 mg dl-1 after fasting and i.v. infusion,
respectively. The corresponding areas
under the concentration-time profiles (AUC)
were 1767 +/ -549, 1619 +/- 760 1270 +/- 406 mg dl-1 min
after fat, CHO, and
protein-rich meals compared with 3210
+/- 527
and 4786 +/- 446 mg dl-1 min after fasting and i.v. infusion,
respectively. The time
required to eliminate ethanol from
the blood
was shortened by 1-2 h in the fed-state. CONCLUSIONS:
Drinking ethanol after eating
a meal, regardless of the nutritional
composition, decreases the systemic availability of ethanol.
Because gastric emptying is slow and
more prolonged with food in the
stomach, the
delivery of ethanol to the duodenum and the liver will be
highly variable as will the
hepatic clearance of ethanol.
Provided that
portal venous BAC remains fairly low and ethanol
metabolizing enzymes are not fully
saturated then part of the dose of
ethanol can
be cleared by hepatic first-pass metabolism (FPM), as one
consequence of
Michaelis-Menten elimination
kinetics.
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Alcohol 1984 Sep-Oct;1(5):385-91
Interindividual variations in the
disposition and
metabolism of ethanol in healthy men.
Jones AW
Forty-eight healthy men each drank a
dose of
ethanol, 0.68 g/kg of body weight, as neat whisky at about
09.00, after fasting
overnight. The drink was finished
within 20
min and the concentrations of ethanol in samples of capillary
blood were determined at
30-60 min intervals for 7 hr. Rectilinear
regression lines were fitted to the elimination phase of blood
concentration time profiles and
blood-ethanol parameters were
calculated as
described by Widmark. In 23, 14, 8 and 3 subjects the peak
blood ethanol
concentrations were reached at 30,
60, 90 and
120 min timed from starting to drink. The highest
concentration of ethanol in blood was
0.92 +/- 0.022 mg/ml (mean +/- SE)
and the
coefficient of variation (CV) was 16.8%. The blood
concentration of ethanol
extrapolated to zero-time was 0.98
+/- 0.009
mg/ml (CV = 6.5%) and the apparent volume of distribution
(Vd) was 0.695 +/-
0.0064 L/kg (CV = 6.4%). The rate of ethanol
elimination from blood was 0.126 +/- 0.0018 mg/ml/hr (CV =
9.9%) and the body
clearance was 87.5 +/- 1.1 mg/kg/hr
(CV =
8.7%). The apparent volume of distribution of ethanol was
inversely related to the
subject's body weight (r = -0.59 +/-
0.118, p
less than 0.001). The elimination rate from blood was lower in
those subjects with larger
distribution volume; the parameters were
negatively correlated (r = -0.52 +/- 0.126, p less than 0.001).
The results show that
blood-ethanol parameters calculated according
to Widmark's method have low intersubject variability when
the dose of ethanol
administered and the condition of the test
subjects are carefully controlled.
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Chronobiologia 1985 Apr-Jun;12(2):137-44
Ethanol pharmacokinetics in healthy man:
Michaelis-Menten parameters and the circadian rhythm.
Minors DS, Waterhouse JM
Eleven presumed healthy subjects
ingested in
random order 3 different doses of ethanol (0.4, 0.6, 0.8 g X
kg body weight-1) at 4
different times of day (0600, 1200, 1800,
0000). The rates of ethanol metabolism were measured by
calculating the rate of decline of
the linear portion of a plot of urinary
concentration of ethanol against time (making correction for
the ratio of ethanol in blood and
urine). The rate of metabolism
depended upon
the dose of ethanol ingested and the peak concentration of
urinary ethanol. The results
lend further support to the view that the
metabolic removal of ethanol can be described by
Michaelis-Menten kinetics. Estimates of the
Michaelis-Menten parameters Km and Vmax
were made by considering the curvilinear portion of the decay
curve at low
concentrations. The values of these
varied with
time of ethanol ingestion; in particular, variation in Vmax can
substantially account for
the circadian rhythm of ethanol metabolism
that had been measured previously.
Both ethanol and its major metabolite acetaldehyde can bind to
proteins in
the blood and liver and other tissues. This is what causes a lot
of the
damage from ethanol drinking. I don't know if it is known how long
detectable acetaldehyde adducts from a single dose of ethanol
are present.
Here is one article about rats given ethanol routinely:
Alcohol Alcohol 2000 Mar-Apr;35(2):164-70
Comparison of the formation of proteins
modified by direct and indirect ethanol metabolites in the
liver
and blood of rats fed the
Lieber-DeCarli liquid
diet.
Worrall S, de Jersey J, Wilce PA
Alcohol Research Unit, Department of
Biochemistry, University of Queensland, Queensland 4072,
Australia.
It has been proposed that proteins
modified by
ethanol metabolites, such as acetaldehyde (AcH) or
alpha-hydroxyethyl radicals (HER)
may be an important step in the
aetiology of
alcoholic liver disease. Furthermore, it has also been suggested
that these modified
proteins may act as a marker of
ethanol intake.
In this study, we have measured the generation of various
types of modified proteins in
the liver and blood of ethanol-fed rats.
Multiple types of protein modification were observed in the
livers of the ethanol-fed rats. In
each case, the level of modification increased
over the first 6 weeks of ethanol feeding, but reached a plateau
by 10 weeks. In contrast
to the liver, elevated levels of proteins
modified by malondialdehyde were not seen in the plasma of
ethanol-fed animals, whereas
elevated levels of modification due
to AcH and
HER were observed. In haemolysates from these animals, only
modification due to
AcH was seen. Further investigation
of the
modification of plasma proteins showed that albumin, a
protein produced in the liver,
carried all the types of modification
investigated, whereas immunoglobulin G, a protein derived
from an extra-hepatic source, only
carried modifications due to
acetaldehyde. This
study demonstrates for the first time that modification of
plasma proteins by ethanol
metabolites can occur at both intra- and
extra-hepatic sites.
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