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Chemical Compound Review

Levadone     (6R)-6-dimethylamino-4,4- diphenyl-heptan-3...

Synonyms: Levothyl, Polamivet, Levomethadone, L-Polamidon, l-Methadone, ...
 
 
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High impact information on L-Polamidon

  • Confidence intervals for all three were within the no-effect or bioequivalence range of 0.80-1.25 for (R)-methadone [1].
  • OBJECTIVES: To determine if atazanavir, a once-daily protease inhibitor and moderate inhibitor of P450 CYP3A4, exhibited pharmacokinetic interactions with (R)-methadone [1].
  • Voriconazole increased the steady-state exposure of pharmacologically active enantiomer (R)-methadone: the mean area under the concentration-time curve from 0 to 24 h (AUC(0-24)) was increased by 47.2% (90% confidence intervals [CI]: 37.7%, 57.4%), and the mean peak concentration (C(max)) was increased by 30.7% (90% CI: 22.2%, 39.8%) [2].
  • Paroxetine increases steady-state concentrations of (R)-methadone in CYP2D6 extensive but not poor metabolizers [3].
  • On ROC analysis, AUC for daily dose (0.77, 95% CI 0.68-0.87), dose/bodyweight (0.76, 95% CI 0.66-0.85), (R)-methadone (0.73, 95% CI 0.63-0.84) and (R,S)-methadone concentration (0.70, 95% CI 0.59-0.81) did not differ significantly [4].
 

Associations of L-Polamidon with other chemical compounds

 

Gene context of L-Polamidon

  • Based on studies with isoform-selective chemical inhibitors and expressed enzymes, CYP3A4 was the predominant enzyme involved in the metabolism of (R)-methadone [5].
 

Analytical, diagnostic and therapeutic context of L-Polamidon

  • Blood samples were analysed by HPLC for plasma morphine and R-(-)-methadone concentrations [6].
  • The results support the use of therapeutic drug monitoring of (R)-methadone in cases of continued intake of illicit opiates [7].
  • Thresholds with specificity near 90% (dose 140 mg/day; (R)-methadone 250 ng/ml; (R,S)-methadone 500 ng/ml) may help guide dose titration for patients continuing to use illicit opiates [4].

References

  1. Lack of an effect of atazanavir on steady-state pharmacokinetics of methadone in patients chronically treated for opiate addiction. Friedland, G., Andrews, L., Schreibman, T., Agarwala, S., Daley, L., Child, M., Shi, J., Wang, Y., O'Mara, E. AIDS (2005) [Pubmed]
  2. Pharmacokinetic Interaction between Voriconazole and Methadone at Steady State in Patients on Methadone Therapy. Liu, P., Foster, G., Labadie, R., Somoza, E., Sharma, A. Antimicrob. Agents Chemother. (2007) [Pubmed]
  3. Paroxetine increases steady-state concentrations of (R)-methadone in CYP2D6 extensive but not poor metabolizers. Begré, S., von Bardeleben, U., Ladewig, D., Jaquet-Rochat, S., Cosendai-Savary, L., Golay, K.P., Kosel, M., Baumann, P., Eap, C.B. Journal of clinical psychopharmacology. (2002) [Pubmed]
  4. Therapeutic thresholds in methadone maintenance treatment: a receiver operating characteristic analysis. Hallinan, R., Ray, J., Byrne, A., Agho, K., Attia, J. Drug and alcohol dependence. (2006) [Pubmed]
  5. Involvement of CYP3A4, CYP2C8, and CYP2D6 in the metabolism of (R)- and (S)-methadone in vitro. Wang, J.S., DeVane, C.L. Drug Metab. Dispos. (2003) [Pubmed]
  6. Methadone maintenance patients are cross-tolerant to the antinociceptive effects of very high plasma morphine concentrations. Athanasos, P., Smith, C.S., White, J.M., Somogyi, A.A., Bochner, F., Ling, W. Pain (2006) [Pubmed]
  7. Plasma concentrations of the enantiomers of methadone and therapeutic response in methadone maintenance treatment. Eap, C.B., Bourquin, M., Martin, J., Spagnoli, J., Livoti, S., Powell, K., Baumann, P., Déglon, J. Drug and alcohol dependence. (2000) [Pubmed]
 
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