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

• In recombinant CYP3A4, the metabolic clearance of (R)-methadone was about 4-fold higher than that of (S)-methadone [5].

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