Method for quantifying alcohol catabolism

The method for quantifying Alcohol Breakdown Activity (ABA) in humans in vivo is developed to determine an efficiency of alcohol catabolism for any given individual. Unlike other related methods, Index-K uses a biological regularity of ABA and employs a third dimension for integrating the multiple pharmacokinetical data into a single value. As expected, it allows for the discrimination between human differences, including gender and personal levels of alcohol dependency. Its use of pharmacokinetical data from ethanol catabolism makes it absolutely specific to alcohol--a major cause of alcohol disorder. This feature allows us to help diagnose alcoholism even in cases where traditional methods used to evaluate harmful alcohol consumption have failed.

BACKGROUND OF THE INVENTION 
Measuring the amount of an alcohol (ethanol) in humans is routinely done 
for a variety of scientific, legal and medical reasons. One of the most 
important reasons is to determine the effective biological marker to 
alcoholism, which affects more than 10 percent of the American adult 
population. A common method of measurement is the Blood (or Breath) 
Alcohol Concentration (BAC). However, no single dependent variable has 
been proposed as a result of such measurements, which can be used as a 
pharmacokinetic biological marker of alcoholism. Moreover, the studies 
performed in the past 50 years have been inconclusive on such factors as 
ethnic background, gender, or participants' stage of alcohol dependency. 
One reason for this failure is that existing pharmacokinetic data 
evaluation methods use a two-dimensional approach which takes into account 
only the concentration of the alcohol versus time. A second reason is a 
different approach taken to the mode of alcohol intake. 
The present invention benefits from the standardized alcohol intake, while 
expanding on the BAC approach by utilizing a multidimensional way of 
managing pharmacokinetical data. This is done by considering specific 
enzymatic body actions multiplied by other mechanisms of alcohol 
elimination to determine individual differences in Alcohol Breakdown 
Activity (ABA). The internal regularity of the ABA nature is then employed 
in an instrument termed the Index-K to provide eventually new diagnostic 
tool for alcoholism as set forth in this specification. 
DESCRIPTION OF THE PRIOR ART 
Testing devices relating to alcohol consumption are well known. Many are 
based on readings taken from the subject's breath. For example, in U.S. 
Pat. No. 3,823,601 to Hoppesch, catalytic and semiconductor detector 
elements respond differently to alcoholic and non-alcoholic breath. A 
predetermined breath alcohol concentration could be indicated by an 
electronic response. In U.S. Pat. No. 4,770,026 to Wolf, breath alcoholic 
content is determined by measuring flow of electrons obtained from 
oxidation of breath alcohol on the surface of the fuel cell. An infrared 
sensing device is used for determining the concentration of alcohol in 
deep lung breath and alveoli from the breath sample in U.S. Pat. No. 
5,376,555 to Forrester et al. And in U.S. Pat. No. 5,443,794 to Williams, 
a volatile component concentration in the gas, such as breath with alcohol 
contamination, is measured. The apparatus is particularly suited for 
breath testing, to see that breath alcohol concentration does not exceed 
legal limits. The present invention seeks to quantify alcohol catabolic 
activity in humans using the readings from repeat measurements of body 
alcohol concentration and employing a new method for managing 
pharmacokinetical data especially designed for this purpose as set forth 
herein. 
SUMMARY OF THE INVENTION 
An innovative Index-K is used to help in diagnosing an alcohol disorder in 
humans by taking into account individual differences in Alcohol Breakdown 
Activity (ABA). 
Using the Index-K instrument, a variety of pharmacokinetical data is 
integrated into a single value which is defined as the ratio between 
descending Area Under a plotted Curve (AUC) and the ascending AUC for a 
pharmacokinetical curve. This ratio presents the individual's quantitative 
assessment of the efficiency of ABA over displaying commensurability of 
the alcohol elimination power by virtue of the protection barriers for 
alcohol absorption. When the values of the of Index-K of 5.89 or higher, 
compare to non-alcoholic male subjects having a value of 2.74, there is a 
quite reasonable, positive association with alcohol disorder. 
It is the primary objective of the present invention to provide the method 
for quantitatively determining a person's efficiency of alcohol 
catabolization. 
Another objective is to provide a new diagnostic tool for 
alcoholism--finally, entirely specific to ethanol. 
Yet another objective is to determine an individual's biological verge 
between relatively "safe" and pathological consumption of alcohol. 
A final objective is to emphasize the different way female humans process 
alcohol from non-alcoholic males. 
These objectives and advantages of the present invention will become 
apparent to readers after considering the ensuing description and 
accompanying drawings.

DESCRIPTION OF THE PREFERRED EMBODIMENT 
Today the evaluation of harmful alcohol consumption is based on an unclear 
quantitative definition of hazardous drinking which is corroborated by the 
elevation of the levels in liver blood tests with positive scores on the 
CAGE (Cut down drinking, Annoyed, felt Guilty, needed Eye-opener) and 
Short Michigan Alcoholism Screening Test (SMAST) questionnaires. This 
assessment is quite imprecise because similar doses of alcohol affect 
people differently. At the same time the blood markers (e.g., SGOT, or 
Aspartate aminotransferase; .tau.GGT or .tau.-Glutamyltransferase; SGPT or 
Alanine aminotransferase, etc.) are not specific for alcohol. Also, the 
questionnaires identification is rather subjective. 
Measured and counted pharmacokinetic changes have produced no single 
dependent variable which can be used as a biological marker of alcoholism. 
This is due to the fact that existing methods of evaluation of 
pharmacokinetical data are strictly two-dimensional; namely, the 
concentration of alcohol versus time. Such two-dimensional quantification 
of alcohol pharmacokinetic data makes subgroup differentiation extremely 
difficult and precludes even a comparison (e.g., BAC versus Transdermal 
Alcohol Level--TAL) applied to a single individual during the same 
experimental session. The present invention seeks to use an innovative 
pharmacokinetical Index-K which utilizes an additional criterion 
accounting for individual differences in Alcohol Break Down Activity 
(ABA). 
It is well known that catabolism of alcohol in the human body depends 
primarily upon specific enzymatic activity, mainly Alcohol Dehydrogenase 
(ADH), which begins converting ethanol in liver to such final products as 
carbon dioxide and water. In addition, approximately one-fifth of consumed 
alcohol is destroyed by the Microsomal Ethanol-Oxidation System (MEOS). 
Also, it is well known that chronic drinking will make for a less 
efficient MEOS mechanism to destroy the alcohol consumed. Other factors, 
such as some sexual hormones which influence another extrahepatic way of 
alcohol catabolism by mucosal gastric ADH activity, are also known. These 
factors, and other still-unknown mechanisms, are activated during ABA and 
proceed through at least three pharmacokinetical phases: i.e., absorption, 
distribution and elimination. That is why with ethanol, a strongly 
hydrophilic substance with a relatively low molecular weight, the 
distribution occurs almost immediately within the absorption phase. 
Because alcohol has a comparatively low chemical reactivity, a biochemical 
neutralizing process (elimination phase) needs more time and energy than 
absorption and distribution phases. Consequently, as shown in FIG. 1, the 
Area Under the Curve (AUC) for the elimination phase (the right, greater 
subtriangle obtained by dividing the main triangle with a bisecting line) 
is always larger than the AUC for the others two phases (the left, lesser 
subtriangle). Even though ethanol elimination begins at very outset of 
consumption, formally the process breaks out from an apex into a 
pharmacokinetical curve--the break point of a neutralizing reaction 
against extreme absorption-distribution action. This specific 
physiological-pharmacokinetic feature has been used to implement the 
present invention because the Index-K is defined as the ratio of AUC 
elimination to AUC absorption-distribution. The FIG. 1 curves show 
oversimplified graphic representation for two possible ways (triangle or 
trapezium) of alcohol catabolism in humans over time, where: 
AUC.sub.abs-distr is the absorption-distribution of ethanol and is equal to 
the AUC under the ascending part of the curve; 
AUC.sub.postabs +AUC.sub.distr is a sum of the postabsorption and 
distribution of ethanol and is equal to the AUC between the ascending and 
descending part of the plotted curve. Because most pharmacokinetical cases 
have a triangle-like shape for the curve, it obviously has no value. 
However, if the value occurs (in a case with a trapezium-like shape for 
the curve) it disregards from calculation, because proportional 
representation for this internal rectangular-like composite AUC is the 
same as the Index-K value; 
and AUC.sub.elim is the elimination of ethanol and is equal to the AUC 
under the descending part of the pharmacokinetical curve. 
To verify the results, after ethanol consumption, BAC levels were 
repeatedly measured by INTOXIMETER EC/IR 3000, until two successive zero 
BAC measurements were obtained. Because the consumed alcohol was 
eliminated through the skin as well as through the lungs, mucous membranes 
and kidneys, the Transdermal Alcohol Level (TAL) was simultaneously 
measured in some cases with BAC by a wearable device, the Transdermal 
Alcohol Sensor/Recorder (TAS). A special electrochemical membrane measured 
oxidation by transdermal ethanol. The resulting current measured is 
expressed in micro Amperes (.mu.A) and was automatically multiplied by 35 
for TAS#37; by 40 for TAS#34, TAS#39, or by 45 for TAS#33 depending on 
type of construction for the device. 
The present invention allows us to characterize the internal body 
regularity of Alcohol Breakdown Activity (ABA) even when taken into 
consideration the numerous pharmacokinetic measurements obtained using 
different methods on the same individual. As the data from FIG. 2 
indicate, values obtained for Index-K remained relatively constant 
(1.9.div.1.97), despite a 2.7-fold variation in the amplitude of the other 
curves. It also equalized the 1.9-fold variation of the "elimination time" 
and the 1.7-fold variation of the "time to peak" differences, which happen 
to be a deadly snare for two-dimensional evaluation methods. This suggests 
conformity with an internal law for the catabolism of alcohol in a given 
subject. The following table of results describes the FIG. 2 curves: 
TABLE 1 
______________________________________ 
METHOD: Breath Alcohol 
Transdermal Alcohol Levels 
Concentration 
(different body location) 
EQUIPMENT: 
Intoximeter 3000 
TAS#33 TAS#39 
DATA: 
Elimination time 
132' .gtoreq.218' 
.gtoreq.220' 
Time to peak 
40' 74' 60' 
Peak value 
31 (mg/dl) 29.91 (.mu.Ax45) 
79.0 (.mu.Ax40) 
Peak delay time 
-- 34' 20' 
Elimination delay 
-- .gtoreq.86' 
.gtoreq.88' 
AUC before peak 
692 993.54 2301.63 
AUC after peak 
1346.997 1890.076 4543.425 
Integrated AUC 
2162.997 2883.615 6845.058 
Index-K 1.95 1.9 1.97 
______________________________________ 
A similar example for the standardized alcohol intake is presented in FIG. 
3 where curves yielded the following tabular results: 
TABLE 2 
______________________________________ 
METHOD: Breath Alcohol 
Transdermal Alcohol Levels 
Concentration 
(different body location) 
EQUIPMENT: 
Intoximeter 3000 
TAS#34 TAS#37 
DATA: 
Elimination time 
294' 326' 374' 
Time to peak 
66' 92' 108' 
Peak value 
89 (mg/dl) 127.4 (.mu.Ax40) 
90.78 (.mu.Ax35) 
Peak delay time 
-- 26' 42' 
Elimination delay 
-- 34' 80' 
AUC before peak 
4011 6261.78 4636.25 
AUC after peak 
9118.053 14674.71 11680.25 
Integrated AUC 
13129.05 20936.48 16316.45 
Index-K 2.27 2.34 2.5 
______________________________________ 
BAC tests were conducted on 83 volunteer individuals, 48 of whom were 
non-alcoholic males, 27 of whom were non-alcoholic females and 8 of whom 
were alcoholic males. A standardized alcohol intake was administered and 
an analysis of obtained data indicated about twice the highest ratio of 
the value of Index-K between alcoholic 5.89 (standard 
deviation-s.d.=2.02), and non-alcoholic drinkers 2.73 (s.d.=0.78) with 
probability-p&lt;0.001. This, even in the three cases, were traditional 
methods of evaluation, such as CAGE, SMAST questionnaires and SGOT, 
.tau.GGT, SGPT liver tests of harmful alcohol consumption, were used have 
failed. 
Ethanol was consumed in a solution made of 95% grain alcohol to 10 parts by 
volume of cold orange juice. This dose was divided into three equal parts. 
Each part of the prepared alcohol cocktail was slowly ingested over of 
five-minute periods (for a total of 15 minutes). 
The BAC readings used in tables 1 and 2 were obtained using breath samples 
taken with the INTOXIMETER EC/IR 3000 made by Intoximeters, Inc. of St. 
Louis, Mo. This device has a rated accuracy of .+-.0.001 (1 mg/dl). The 
machine was reprogrammed to increase ethanol values by five percent from 
factory settings to more accurately reflect actual BAC. Deep lung breath 
samples are highly correlated with blood alcohol concentration measured by 
Gas Chromatography (GC). Our laboratory comparison of a breath by 
breathalyzer and blood alcohol concentration measured at the same time by 
GC showed a blood/breath ratio of 0.994 with a correlation of 0.99. 
The Transdermal Alcohol Levels (TAL) were estimated by the Transdermal 
Alcohol Sensor/Recorder (TAS). These devices were made by Giner Inc. of 
Waltham, Mass. The TAS is a novel, experimental device consisting of an 
electrochemical sensor that detects ethanol, and a data 
acquisition-recording circuitry. During the test, the sensor was placed 
over the skin surface and continuously oxidizes excreted ethanol. The 
oxidation current provides a direct measurement of local ethanol vapor 
concentration. 
Despite the similar peak in the BAC for non-alcoholic male 69.7 (s.d.=8.49 
) and female 68.2 (s.d.=8.98) tested individuals, the method is capable of 
detecting a gender difference in ABA. The value of Index-K for women is 
3.59 (s.d.=1.07) compared to the Index-K for non-alcoholic men of 2.74 
(s.d.=0.77). The probability of &lt;0.001 suggests that a female's protective 
barrier against alcohol in general is weaker than the non-alcoholic male. 
The method constitutes on a way to quantify ABA in humans which allows for 
separation between relatively "safe" and harmful alcohol consumption for 
any given individual. In the present recognition, based on the BAC data 
from 83 experimental subjects, the verge for "safe" alcohol consumption 
would be a particular value for the Index-K of 3.4 or less. 
Although the Index-K and the method of using the same according to present 
invention has been described in foregoing specification with considerable 
detail, it is to be understood that modifications may be made to the 
invention which do not exceed the scope of the appended claims and 
modified forms of the present invention done by other skilled in the art 
to which the invention pertains will be considered infringements of this 
invention when those modified forms fall within the claimed scope of this 
invention. 
Also, because the proposed method is universal and interest in 
quantificaiton of catabolism for substances other than ethanol in human 
body will increase in future studies, be advised that applying the Index-K 
concept in such research without the inventor's assent will be considered 
encroachment on the author's rights.