2/12/2019. Direct biomarkers of alcohol consumption in professionals health programs. Objectives. IPN/PRN Annual Conference and Evaluator Training

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1 IPN/PRN Annual Conference and Evaluator Training Direct biomarkers of alcohol consumption in professionals health programs Scott A. Teitelbaum, M.D. Gary M. Reisfield, M.D. Division of Addiction Medicine Department of Psychiatry University of Florida College of Medicine 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. 09/23/15 1

2 Unchanged in breath, urine, sweat Alcohol metabolism 5% Ethanol 95% Alcohol dehydrogenase (ADH) Acetaldehyde Aldehyde dehydrogenase (ALDH) Adapted from: Karch S. Drug Abuse Handbook, 2007 Acetate BrAC monitoring BrAC and zero order kinetics After 1 h After 2 h After 3 h After 4 h After 5 h

3 TAC Monitoring Unchanged in breath, urine, sweat 0.1% 5% Ethyl glucuronide (EtG) 0.1% Ethanol Ethyl sulfate (EtS) 95% Alcohol dehydrogenase (ADH) Acetaldehyde Aldehyde dehydrogenase (ALDH) Adapted from: Karch S. Drug Abuse Handbook, 2007 Acetate 3

4 Urinary EtG/EtS limitations: 1 Clinical false positive Clinical false negative EtG 1. Incidental exposures 2. UTI: E. coli* 1. Dilution 2. UTI: E. coli (with β-glucuronidase) C. sordellii (with β-glucuronidase) 3. UGT 1A1 polymorphism (?) EtS 1. Incidental exposures 1. Dilution *In presence of alcohol (i.e., alcohol in urine or yeast (e.g., Candida albicans) + glucose) 4

5 EtG/EtS limitations: 2 Alcohol dose group Low (n=18) Medium (n=18) High (n=17) Target BAC (g/dl) EtOH dose, mean (g) Number of standard drinks Peak BAC (g/dl) EtG, mean time (hrs) to final 100 ng/ml EtG, mean time (hrs) to final 500 ng/ml 11K ng/ml 89K ng/ml Alcohol dose group 200K ng/ml Low (n=18) Medium (n=18) High (n=17) Jatlow PI, et al. Alcohol Clin Exp Res 2014;38: Suggested EtGcut-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 5

6 Suggested EtScut-off concentrations to detect any alcohol consumption [EtG] 4 Unchanged in breath, urine, sweat 0.1% 5% Ethyl glucuronide (EtG)? 0.1% Ethanol Phospholipase D (PLD) Phosphatidylethanol (PEth) Ethyl sulfate (EtS) 95% Alcohol dehydrogenase (ADH) Acetaldehyde Aldehyde dehydrogenase (ALDH) Adapted from: Karch S. Drug Abuse Handbook, 2007 Acetate 6

7 Phosphatidylcholine choline water ethanol choline PLD choline Phosphatidic acid ethanol Phosphatidylethanol (PEth) Adapted from: Isaksson A, et al. Drug Testing and Analysis 2011; 3: PEth 16:0/18:1 Phosphatidyl ethanol Daily alcohol consumption n=44 Grams/day Drinks/day Women Men

8 n=23 n=21 14 (< ) 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: Piano MR, et al. Alcohol Alcohol 2015;50: Classification Abstainers (n=23) Moderate drinkers (n=22) Binge drinkers* (n=58) Definitions 1 drink in past month M: 3 drinks, 2x/week F: 2 drinks, 2x/week M: 5 drinks, 2x/week F: 4 drinks, 2x/week 8

9 4.1 drinks/week 16.5 drinks/week Piano MR, et al. Alcohol Alcohol 2015;50: Our conclusions based on extant literature 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 9

10 1,040 IMEs uetg, uets, PEth measured 1 positive results New evaluations Percentage of IMEs with positive results at PEth 20 and different EtG/EtS cutoff concentrations New evaluations Mdn: 58 ng/ml Mdn: 83 ng/ml Mdn: 688/47 ng/ml Mdn: 1,842/218 ng/ml Mdn: 1,384 ng/ml Mdn: 3,567 ng/ml 58 4 Evaluees with a single positive biomarker 31 Mdn: 51 ng/ml 73 Mdn: 41 ng/ml 12% 19 EtS100 10

11 Percentage of PEth 20 - and EtG /EtS positive participants according to reason for referral 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% n=57 Mdn: 51 ng/ml Mdn: 69 ng/ml 81% 65% 58% Mdn: 310/40 ng/ml Mdn: 687/62 ng/ml 26% 27% 3% Alcohol-related referral (n=31) Non-alcohol-related referral (n=26) PEth EtG100/EtS25 EtG500/EtS100 Percentage of PEth 20 - and EtG /EtS positive participants according to alcohol use disorder history 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Mdn: 55 ng/ml Mdn: 122 ng/ml n=57 86% Mdn: 310/40 ng/ml Mdn: 541/41 ng/ml 76% 43% 28% 14% 11% History of alcohol use disorder (n=36) No history of alcohol use disorder (n=21) PEth EtG100/EtS25 EtG500/EtS100 Role of PEthin the IME 100% PEth providing essential information 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% % 47% PEth (+) PEth (-) 11

12 IMEs with hair EtG 20 testing New evaluations 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 12

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