Dose–Concentration Relationships of Methadone and EDDP in Hair of Patients on a Methadone-Maintenance Program

Mußhoff, Frank; Lachenmeier, Katrin; Lachenmeier, Dirk W.; Wollersen, Heike; Madea, Burkhard

doi:10.1385/fsmp:1:2:097

Cited by 10 publications

(6 citation statements)

References 23 publications

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“…The sensitivity analysis data for tolerant users are additionally shown in Figure 1 – 3 based on the ratio between no-tolerance and high tolerance dosage as shown in Table 2 27 37 42 43 44 45 46 47 48 49 50 51 52 53 54 . Even though the general results remain stable (i.e.…”

Section: Resultsmentioning

confidence: 99%

Comparative risk assessment of alcohol, tobacco, cannabis and other illicit drugs using the margin of exposure approach

Lachenmeier

Rehm

2015

Sci Rep

Self Cite

167

106

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A comparative risk assessment of drugs including alcohol and tobacco using the margin of exposure (MOE) approach was conducted. The MOE is defined as ratio between toxicological threshold (benchmark dose) and estimated human intake. Median lethal dose values from animal experiments were used to derive the benchmark dose. The human intake was calculated for individual scenarios and population-based scenarios. The MOE was calculated using probabilistic Monte Carlo simulations. The benchmark dose values ranged from 2 mg/kg bodyweight for heroin to 531 mg/kg bodyweight for alcohol (ethanol). For individual exposure the four substances alcohol, nicotine, cocaine and heroin fall into the “high risk” category with MOE < 10, the rest of the compounds except THC fall into the “risk” category with MOE < 100. On a population scale, only alcohol would fall into the “high risk” category, and cigarette smoking would fall into the “risk” category, while all other agents (opiates, cocaine, amphetamine-type stimulants, ecstasy, and benzodiazepines) had MOEs > 100, and cannabis had a MOE > 10,000. The toxicological MOE approach validates epidemiological and social science-based drug ranking approaches especially in regard to the positions of alcohol and tobacco (high risk) and cannabis (low risk).

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Section: Resultsmentioning

confidence: 99%

Comparative risk assessment of alcohol, tobacco, cannabis and other illicit drugs using the margin of exposure approach

Lachenmeier

Rehm

2015

Sci Rep

Self Cite

167

106

View full text Add to dashboard Cite

show abstract

“…Several studies have been conducted, which look at adult methadone users on maintenance programs. In one, hair concentrations of methadone from low therapeutic doses (15–20 mg) were as low as 0.25 ng/mg . However, other scientific papers have recorded much higher concentrations of methadone from small therapeutic doses.…”

Section: Resultsmentioning

confidence: 99%

Interpretation of Pharmaceutical Drug Concentrations in Young Children's Head Hair

Chatterton

Turner²,

Klinger³

et al. 2013

Journal of Forensic Sciences

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Three separate cases of child administration of prescription drugs are described. Following liquid-liquid extraction, high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to identify and quantify methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenyl-1-pyrrolidine (EDDP), tramadol, amitriptyline, and nortriptyline in children's hair. The children's age ranged from 14 months to 7 years; in all three cases, the drug in question was detected in more than one section of hair. Methadone was detected in the concentration range of 0.65-0.99 and 0.04-0.4 ng/mg; tramadol was detected in the concentration range of 1.5-2.2 ng/mg; amitriptyline and nortriptyline were detected in the concentration range of 0.18-1.06 and 0.38-2.0 ng/mg, respectively. In each case, the children's parents admitted to or were found guilty of drug administration to the child. These cases demonstrate the added value of hair testing and emphasize the importance of using hair samples to complement conventional analyses.

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“…In the hair, the reported ranges of methadone concentrations were between 0.25 and 80.8 ng/mg; the ranges of EDDP between 0.05 and 7.76 ng/mg. The corresponding ratios in those studies (methadone-to-EDDP) were calculated as between 1.4 and 32.2 [ 9 , 23 – 25 ]. Both ranges and ratios were in line with the results from our study (see Tables 4 and 5 ).…”

Section: Discussionmentioning

confidence: 99%

Evidence for the transfer of methadone and EDDP by sweat to children’s hair

et al. 2021

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In cases where there is a question as to whether children have come into contact with drugs, examinations of their scalp hair are frequently carried out. Positive test results are often discussed in the forensic community due to the various possible modes via which drugs and their metabolites can be incorporated into the hair. These include drug uptake by the child (e.g. oral ingestion or inhalation), but also contamination of hair via contact with the sweat from drug users. In this study, the possibility of methadone and its metabolite EDDP being incorporated into children’s hair by contact with sweat from persons undergoing opiate maintenance therapy (methadone) was examined. The transfer of methadone and EDDP via sweat from methadone patients (n = 15) to children’s hair was simulated by close skin contact of drug-free children’s hair, encased in mesh-pouches, for 5 days. Sweat-collecting patches (hereafter referred to as ‘sweat patches’) were applied to the test persons’ skin. One strand of hair and one sweat patch were collected daily from each patient. Analyses were performed using GC–MS/MS (hair) and LC–MS/MS (serum, sweat patches). After 4 days of skin contact, methadone was detectable in the formerly drug-free hair strands in all 15 study participants. EDDP was detectable in 34 of 75 hair strands, with the maximum number of positive results (11 EDDP-positive hair strands) being detected after 5 days. These results show that transfer of methadone and EDDP to drug-free hair is possible through close skin contact with individuals taking part in methadone substitution programmes. A correlation between serum concentration, sweat concentration and substance concentration in hair strands could not be demonstrated, but a tendency towards higher concentrations due to longer contact time is clearly evident.

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Dose–Concentration Relationships of Methadone and EDDP in Hair of Patients on a Methadone-Maintenance Program

Cited by 10 publications

References 23 publications

Comparative risk assessment of alcohol, tobacco, cannabis and other illicit drugs using the margin of exposure approach

Comparative risk assessment of alcohol, tobacco, cannabis and other illicit drugs using the margin of exposure approach

Interpretation of Pharmaceutical Drug Concentrations in Young Children's Head Hair

Evidence for the transfer of methadone and EDDP by sweat to children’s hair

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