Methadone maintenance treatment: is it possible to adapt the daily doses to the metabolic activity of the patient?
Controversy still exists concerning the proper daily dose of methadone to be used in opiate dependency treatment. Because it is admitted that serum methadone concentration may be significantly correlated with the amount of drug available at the receptor level, it could be interesting to predict the methadone daily doses necessary to reach such a serum concentration. The authors have attempted to correlate the serum methadone level with the daily intake, considering the metabolic activity of the patients. A poor correlation was found between methadone doses and methadone serum concentrations (r2 = 0.0409, p = 0.048). The test used to determine the metabolic activity of patients is the 6-OH cortisol/17-OH corticosteroids ratio in urine. This urinary 6-OH cortisol/17-OH corticosteroids ratio was tested because cortisol is metabolized through the same P450 cytochromes as methadone, namely cytochrome P450 3A4. This determination could be of interest because it could be tested before methadone administration to predict optimal doses. But when the authors tried to correlate the methadone serum concentration with the steroid ratio, they failed to find a significant correlation (r2 = 0.0046, N.S.), even when they took into account the daily doses (r2 = 0.0015, N.S.), most probably because of some limitations of the cortisol ratio.
Charlier
C
C
Laboratory of Toxicology, University Hospital, Liege, Belgium.
Dessalles
M C
MC
Plomteux
G
G
D000328:Adult; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008691:Methadone / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use*; D006899:Mixed Function Oxygenases / Q000235:genetics; D009294:Narcotics / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use*; D009293:Opioid-Related Disorders / Q000235:genetics / Q000378:metabolism* / Q000534:rehabilitation*; D010641:Phenotype
D009294:Narcotics; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D008691:Methadone; D006854:Hydrocortisone