3/17/2019
Direct biomarkers of alcohol consumption in professionals health programs Scott Teitelbaum, FAAP, DFASAM Pottash Professor in Psychiatry and Neuroscience Department of Psychiatry University of Florida Division Chief of Addiction Medicine Medical Director, Florida Recovery Center
Special Thanks to Colleagues Dr. Gary Reisfield and Dr. Shannon Large
Objectives
• Name three direct biomarkers of alcohol consumption. • Describe the temporal windows of detection for alcohol and its direct biomarkers. • Identify the sources of clinical false positive and clinical false negative results in alcohol biomarker testing. • Identify the most commonly observed direct alcohol biomarker in participants and new evaluees in Florida’s professionals health programs.
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09/23/15
AlcoholUnchanged inmetabolism breath, urine, sweat
≤5%
Ethanol
≥95% Alcohol dehydrogenase (ADH)
Acetaldehyde
Aldehyde dehydrogenase (ALDH)
Acetate Adapted from: Karch S. Drug Abuse Handbook, 2007
BrAC monitoring
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BrAC and zero order kinetics .08 After 1 h .065
After 2 h .050
After 3 h .035
After 4 h .020
After 5 h .005
TAC Monit oring
3 3/17/2019
Unchanged in breath, urine, sweat
≤5% ≤0.1%
Ethyl glucuronide (EtG)
≤0.1%
Ethanol
Ethyl sulfate ≥95% Alcohol dehydrogenase (EtS) (ADH)
Acetaldehyde
Aldehyde dehydrogenase (ALDH)
Acetate Adapted from: Karch S. Drug Abuse Handbook, 2007
Urinary EtG/EtS limitations: 1
EtG EtS
1. Incidental exposures 1. Incidental exposures “Clinical false 2. UTI: E. coli * positive” 1. Dilution 1. Dilution “Clinical false 2. UTI: E. coli (with β-glucuronidase) negative” C. sordellii (with β-glucuronidase) 3. UGT 1A1 polymorphism (?)
*In presence of alcohol (i.e., alcohol in urine or yeast (e.g., Candida albicans) + glucose)
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EtG/EtS limitations: 2
Alcohol dose group Low ( n=18) Medium ( n=18) High ( n=17) Target BAC (g/dL) 0.02 0.08 0.12 EtOH dose, mean (g) 26.3 57.8 78.8 Number of standard drinks 2 4 6 Peak BAC (g/dL) 0.03 0.09 0.14
89K 200K 11K ng/mL ng/mL ng/mL Alcohol dose group Low ( n=18) Medium ( n=18) High ( n=17) EtG , mean time (hrs) to final 22 ± 5 32 ± 10 37 ± 12 positive @ 100 ng/mL EtG , mean time (hrs) to final 12 ± 5 23 ± 3 26 ± 7 positive @ 500 ng/mL
Jatlow PI, et al. Alcohol Clin Exp Res 2014;38:2056-2065
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Suggested EtS cut-off concentrations to detect any alcohol consumption
[EtG] 4
Suggested EtG cut-off concentrations to detect any alcohol consumption
• Anton (2014): • 100 ng/mL for clinical applications • 500 ng/mL for forensic applications • Jatlow (2014): 100 ng/mL or 200 ng/mL for clinical trials • Lowe (2015): 200 ng/mL for clinical and research purposes • McDonell (2015): • 100 ng/mL for clinical and research purposes • 200 ng/mL for when “minimizing false positive results is essential” • SAMHSA (2012): • 100 ng/mL for confirmation of total abstinence • 100-1,000 ng/mL indicates ethanol consumption or incidental exposures • >1,000 ng/mL confirms ethanol consumption
Unchanged in breath, urine, sweat
≤5% ≤0.1%
Ethyl glucuronide (EtG) ?
≤0.1% Phospholipase D (PLD) Phosphatidylethanol Ethanol (PEth)
Ethyl sulfate ≥95% Alcohol dehydrogenase (EtS) (ADH)
Acetaldehyde
Aldehyde dehydrogenase (ALDH)
Acetate Adapted from: Karch S. Drug Abuse Handbook, 2007
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Phosphatidylcholine
choline
water ethanol PLD choline choline
ethanol Phosphatidic acid Phosphatidylethanol (PEth)
Adapted from: Isaksson A, et al. Drug Testing and Analysis 2011; 3:195-200
PEth 16:0/18:1
Phosphatidyl ethanol
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Daily alcohol consumption n=44 Grams/day Drinks/day Women 16-16.5 1.15 Men 32-33 2.3
n=23 n=21
14 (<3.5-183) ng/mL <3.5 (<3.5-25) ng/mL 13 (<3.5-84) ng/mL 16 (5-120) ng/mL
Kechagias S, et al. Alcohol and Alcoholism 2015;50:399-406
100 ng/mL
35 ng/mL 20 ng/mL
Kechagias S, et al. Alcohol and Alcoholism 2015;50:399-406
8 3/17/2019
Piano MR, et al. Alcohol Alcohol 2015;50:519-525
Classification Definitions
Abstainers (n=23) ≤1 drink in past month
M: ≤3 drinks, ≤ 2x/week Moderate drinkers ( n=22) F: ≤2 drinks, ≤ 2x/week
M: ≥ 5 drinks, ≥ 2x/week Binge drinkers* ( n=58) F: ≥ 4 drinks, ≥ 2x/week
*Average number of past month binges: 7.2 ± 4 Average number of drinks per last binge: 8.3 ± 2 (range: 4-13)
4.1 drinks/week 16.5 drinks/week
Piano MR, et al. Alcohol Alcohol 2015;50:519-525
9 3/17/2019
Our conclusions based on extant literature
• PEth 20 theoretically offers perfect specificity for alcohol consumption • There are large inter-individual variations in PEth kinetics
• PEth 20 can theoretically be detected for >4 weeks after last use • One cannot determine time/quantity of last drink from PEth concentration
• Negative PEth 20 ≠ proof of alcohol abstinence
• Negative PEth 20 is compatible with: • Alcohol abstinence • Daily low-risk (1-2 drinks/day) alcohol consumption
• Positive PEth 20 disproves abstinence • Positive triple-digit PEth indicates heavy alcohol consumption
The roles of phosphatidylethanol (PEth), ethyl glucuronide (EtG), and ethyl sulfate (EtS) in identifying alcohol consumption among participants in professionals’ health programs
Reisfield G, University of Florida, Psychiatry Teitelbaum S, University of Florida, Psychiatry Morrison D, University of Florida, Psychiatry Large S, University of Florida, Psychiatry Jones J, United States Drug Testing Laboratories Inc
1,040 IMEs
• uEtG, uEtS, PEth measured • ≥1 positive results
57 194 On contract New evaluations
10 3/17/2019
Percentage of IMEs with positive results at PEth 20 and/or different EtG/EtS cutoff concentrations On contract New evaluations
Mdn: 58 ng/mL Mdn: 83 ng/mL
Mdn: 688/47 ng/mL Mdn: 1,842/218 ng/mL
Mdn: 3,567 ng/mL 153 40 Mdn: 1,384 ng/mL 120 26 58 4
Evaluees with a single positive biomarker
Mdn: 51 ng/mL
Mdn: 41 ng/mL
31 73 12%
Oncontract 19
EtS100
Percentage of PEth 20 - and EtGEtG 500100/EtS/EtS1 25 -positive participants according to00 reason for referral
n=57 100% Mdn: 51 ng/mL Mdn: 69 ng/mL 90% 81% 80% 70% 65% 58% 60% 50% Mdn: 310/40 ng/mL Mdn: 687/62 ng/mL 40% 26% 30% 27% 20% 10% 3%
Oncontract 0% Alcohol-related referral (n=31) Non-alcohol-related referral (n=26) PEth EtG100/EtS25EtG500/EtS100
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Percentage of PEth 20 - and EtGEtG 500100/EtS/EtS1 25 -positive participants according to alcohol00 use disorder history
100% Mdn: 55 ng/mL Mdn: 122 ng/mL n=57 90% 86% Mdn: 310/40 ng/mL Mdn: 541/41 ng/mL 80% 76%
70%
60%
50% 43% 40%
30% 28%
20% 14% 11% 10%
0% Oncontract History of alcohol use disorder (n=36) No history of alcohol use disorder (n=21) PEth EtG100/EtS25EtG500/EtS100
Role of PEth in the IME
PEth providing essential information 100% 90% 80% 70% 60% 50% 6 10% 40% 30% 20% 27 47% 10% 0% Oncontract PEth (+) PEth (-)
IMEs with hair EtG 20 testing
On contract New evaluations
16 50
31 6 15 1
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Conclusions
1. There is no single ideal biomarker for measuring alcohol abstinence 2. For detecting any recent alcohol use, PEth was the single most important biomarker, but… 3. For detecting any recent alcohol use, PEth combined with EtG/EtS had the greatest yield.
4. With regard to urinary biomarkers, traditional EtG 500 -only screening would have left most very recent alcohol consumption undetected. The greatest yield necessitates EtS testing.
5. Based on very limited evidence, hair EtG 20 offered the lowest yield for detecting alcohol consumption. 6. Best use of biomarkers requires history (days), history (weeks), history (months)!
Additional talking points
• Roles of PEth • In PHP • Early after +EtG • Random • In treatment • Early • Role of mobile BrAC monitoring tools
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