1. Clinical Pharmacokinetics of Alcohol in A CDAT Sample Robert Cohen Consultant Addiction Psychiatrist 9.11.2012

2. Introduction The way the body handles alcohol is of interest to a number of different groups

3. Back calculation of alcohol is based on the assumption that the body clears 1 unit of alcohol per hour (zero order kinetics) Zero order kinetics – same rate of removal however much alcohol left First order kinetics – the more alcohol in the blood stream, the quicker it is removed

4. Limited use of alcohol testing in the clinical setting Result of testing often limited to positive or negative –Though the readings in blood, breath and hair are quantitative and need interpretation

5. Alcohol testing Ethanol (ethyl alcohol) or metabolites can be tested in a variety of matrices –Blood –Breath –Sweat –Urine –Hair Breath alcohol levels closely parallel arterial blood levels Jones & Andersson, For Sci Int 2003;132: 18

6. The breathalyser Presents an easy method to test for alcohol levels Easy to carry out the test Reliable machinery

9. This study Kingston CDAT LDASS

10. The problem of interpreting breathalyser readings When you take a breathalyser reading, you do not know –When the person last drank –How much they drank But you may be able to gain an understanding if you know the rate of elimination, –which you can work out by taking multiple readings This study is a pilot into the start of this question

11. Methods 20 consecutive patients who attended for assessment for alcohol / drug problems and whose breathalyser reading was more than 0.00mg/l Breath alcohol level readings taken at regular intervals Rate of elimination calculated and compared to the concentration A composite made of all the readings

12. TimeBreath alcohol concentration (mg/l) 14:121.69

13. TimeBreath alcohol concentration (mg/l) 14:121.69 14:271.55

14. TimeBreath alcohol concentration (mg/l) Rate of Elimination (mg/l/hr) 14:121.690.56 14:271.55

15. TimeBreath alcohol concentration (mg/l) Rate of Elimination (mg/l/hr) 14:121.690.56 14:271.550.32 14.421.47

17. clearancedistributionabsorption

18. Results 20 patients at the time of audit 10 patients used only alcohol (‘alcoholics’) 10 patients used alcohol on top of methadone (‘drug addicts’) All met the criteria for a clinical ICD-10 diagnosis of mental and behavioural disorder due to use of alcohol, dependent type (F10.2)

19. Results - Demographics AlcoholicsDrug Addicts N10 Male5 (50%)8 (80%) Age – mean (range)50 (38-68)35.9 (26-44) Weekly units of alcohol – mean (range) 133.6 (0-284)202.3 (56-455)

20. Results – Breathalyser Readings AlcoholicsDrug Addicts N10 Total # of readings3244 Range of number of readings per patient 2-62-13 Readings (mg/l)0.04-1.050.03-2.00 Range - reduction rate (mg/l/hour) -0.04-0.58-0.68-1.88 R for reduction rate & alcohol concentration 0.46 (p=0.007)0.43 (p=0.003)

21. All patients

22. Alcoholics Drug Addicts

23. Discussion - findings Alcohol clearance in people with the alcohol dependence syndrome appears to follow first order kinetics rather than zero order kinetics –This is a composite picture of 20 patients, rather than a full study of individuals over the whole of the pharmacokinetic profile (absorption, distribution and clearance) –This is therefore a pilot study, generating a hypothesis for formal testing

24. Discussion – clinical implications Potential to lead to biologically based diagnosis of alcohol dependence Biological support for drinking reduction as a therapeutic step prior to detoxification Possible clinical-biological difference between those only using alcohol and alcohol/opiate users

25. Discussion – clinical implications-1 If there are clinical differences in the pharmacokinetics of alcohol between dependent people and non-dependent people, this may form the basis of a clinical biologically based test for alcohol use disorder, as opposed to history / rating scale based diagnosis This is for future investigation

26. Discussion – clinical implications-2 This work may eventually elucidate the plasma level of alcohol associated with onset of withdrawal symptoms However, clinical observations of patients with low plasma levels (e.g., 0.10mg/l) is mixed –Some show withdrawal symptoms –Others do not

27. Discussion – clinical implications-2 If withdrawal symptoms drive alcohol consumption in dependent patients then more rapid clearance may be lead to greater consumption, thereby creating a vicious circle Helping people reduce consumption rather than attain immediate abstinence may therefore be an appropriate clinical goal as a step prior to detoxification Higher alcohol level Faster alcohol clearance Plasma reduction felt more Greater need to drink

28. Discussion – clinical implications-3 There may be a difference between those who are in addition opiate dependent and those who are only dependent on alcohol –There is some evidence for this (Clarke, JSAT 2006; 30:191) But the findings in this study may also be attributable to the higher level of drinking by opiate dependent patients

29. Thank you for listening robert.cohen@sept.nhs.uk