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Pharmacokinetics of methadone during maintenance treatment: adaptive changes during the induction phase.

Abstract：

:Deuterated methadone (M-d3) and GCMS 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 beta-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 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.

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

Nilsson MI,Anggård E,Holmstrand J,Gunne LM

doi

10.1007/BF00548404

subject

Has Abstract

pub_date

1982-01-01 00:00:00

pages

343-9

issue

4

eissn

0031-6970

issn

1432-1041

journal_volume

22

pub_type

杂志文章

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