ISSN:
1432-1041
Keywords:
methadone
;
opiate addicts
;
pharmacokinetics
;
single and multiple doses
;
stable isotope technology
;
methadone maintenance therapy
;
deuterium technique
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Summary Deuterated methadone (M-d30) and GC-MS were used to study the pharmacokinetics of methadone (M) during the induction stage of methadone maintenance treatment (MMT). A pulse dose of M-d3 was given on Days 1 and 25 of two dosage regimens, one with a continuous 30 mg dose (n=6), and the other with 30 mg for 10 days, followed by 60 mg as the maintenance dose (n=6). Plasma and urinary levels of M and M-d3 were measured throughout and plasma half-lives, oral bioavailabilities and volumes of distribution were calculated from the data of Days 1–2 and 24–26. The oral bioavailability of a methadone solution was found to be between 81 and 95%; elimination half-life in the β-phase varied between 19 and 58 h; the volume of distribution was 4.1±0.65 l/kg; and total body clearance of M was 54–195 ml/min and its renal clearance 3.4–34 ml/min. A consistent finding was a lower urinary pH and increased renal clearance during the first days of MMT as compared with after one month. In 4/12 of the patients dispositional tolerance was developed to methadone during the first month of treatment. The shorter elimination half-lives in those patients probably caused unacceptably high fluctuation in the body content of M during the 24 h dosage interval, and may have interfered therefore, with its therapeutic effectiveness
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00548404
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