Pharmakokinetische Wechselwirkungen illegaler Drogen mit Arzneimitteln

Keil, Sven; Iwersen‐Bergmann, Stefanie; Müller, A.; Andresen‐Streichert, Hilke

doi:10.1007/s00194-013-0935-0

Cited by 2 publications

(1 citation statement)

References 88 publications

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“…For example, Eap and coworkers [4] reported a 17-fold inter-individual variation of blood concentrations for the same dose of S. Iwersen-Bergmann and S. Plattner shared as first authorship methadone. Furthermore, drug-drug interactions by comedication have an impact on the pharmacokinetics of methadone [4][5][6][7][8][9]; in particular, antiretroviral drugs can affect methadone maintenance treatment (MMT) [9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Brain/blood ratios of methadone and ABCB1 polymorphisms in methadone-related deaths

et al. 2021

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Methadone is an opioid that often leads to fatalities. Interpretation of toxicological findings can be challenging if no further information about the case history is available. The aims of this study were (1) to determine whether brain/blood ratios can assist in the interpretation of methadone findings in fatalities; (2) to examine whether polymorphisms in the gene encoding the P-glycoprotein (also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1)), which functions as a multispecific efflux pump in the blood–brain barrier, affect brain/blood ratios of methadone. Femoral venous blood and brain tissue (medulla oblongata and cerebellum) from 107 methadone-related deaths were analysed for methadone by gas chromatography-mass spectrometry. In addition, all the samples were genotyped for three common ABCB1 single nucleotide polymorphisms (SNPs rs1045642, rs1128503, and rs2032582) using ion-pair reversed-phase high-performance liquid chromatography-electrospray ionization mass spectrometry (ICEMS). In nearly all cases, methadone concentrations were higher in the brain than in the blood. Inter-individual brain/blood ratios varied (0.6–11.6); the mean ratio was 2.85 (standard deviation 1.83, median 2.35). Moreover, significant differences in mean brain/blood ratios were detected among the synonymous genotypes of rs1045642 in ABCB1 (p = 0.001). Cases with the T/T genotype had significantly higher brain/blood ratios than cases with the other genotypes (T/T vs. T/C difference (d) = 1.54, 95% CI [1.14, 2.05], p = 0.002; T/T vs. C/C d = 1.60, 95% CI [1.13, 2.29], p = 0.004). Our results suggest that the rs1045642 polymorphisms in ABCB1 may affect methadone concentrations in the brain and its site of action and may be an additional factor influencing methadone toxicity.

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Section: Introductionmentioning

confidence: 99%

Brain/blood ratios of methadone and ABCB1 polymorphisms in methadone-related deaths

et al. 2021

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Intravenous methadone application as a serious risk factor for an overdose death: methadone-related fatalities in Hamburg from 2007 to 2012

Iwersen‐Bergmann¹,

Jungen²,

Andresen‐Streichert³

et al. 2014

Int J Legal Med

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Methadone plays an increasing role in drug-related deaths in Hamburg. To find out whether intravenous application of methadone plays a relevant role in methadone-related deaths, body fluids of all methadone-positive cases (n=130) and three buprenorphine-positive cases where a urine sample was available (n=58+3) were investigated for disaccharides (sucrose and lactose as markers for intravenous methadone abuse). Sixty-four percent of the urine samples of the methadone cases showed positive results for disaccharides (22 times sucrose alone, range 2 to >1,000 mg/L; 6 times lactose and sucrose; and 9 times lactose alone, range 22 to 382 mg/L). The three buprenorphine cases showed positive results for lactose in urine. In blood, it was not possible to detect any disaccharides. Of the 116 fatal methadone intoxications, 49 % were under opiate maintenance treatment (OMT) at the point of death (A-OMT), 30 % were never in OMT (N-OMT) and 21 % were formerly in an OMT, but not at the point of death (F-OMT). Of the deceased in the OMT group, 12 % (n=7) died within the first 2 weeks of treatment, six of them within the first week. Overall, intravenous abuse of methadone plays a relevant role in methadone-related fatal cases of substituted patients and of drug consumers not in therapy. Thus, it is necessary that therapists keep to the statutory regulations and give take-home doses only after at least 6 months of successful therapy and when there is no suspicion of intravenous abuse.

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Pharmakokinetische Wechselwirkungen illegaler Drogen mit Arzneimitteln

Cited by 2 publications

References 88 publications

Brain/blood ratios of methadone and ABCB1 polymorphisms in methadone-related deaths

Brain/blood ratios of methadone and ABCB1 polymorphisms in methadone-related deaths

Intravenous methadone application as a serious risk factor for an overdose death: methadone-related fatalities in Hamburg from 2007 to 2012

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