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Pharmacokinetic and pharmacodynamic interactions in an outpatient maintenance therapy of intravenous heroin users with levomethadone
Author(s) -
SCHALL ULRICH,
PRIES ELLEN,
KATTA TALEB,
KLÖPPEL ACHIM,
GASTPAR MARKUS
Publication year - 1996
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1080/1355621961000124736
Subject(s) - medicine , heroin , pharmacodynamics , pharmacokinetics , drug , benzodiazepine , maintenance therapy , pharmacology , liver function , maintenance dose , methadone maintenance , urine , methadone , receptor , chemotherapy
The plasma levels of 42 patients on a levomethadone maintenance treatment programme for intravenous heroin users were measured before and, respectively, 1, 2 or 4 hours after oral routine administration and related to the individual additional drug usage (detected by urine drug screening), liver function, side‐effects and withdrawal symptoms. In general, accelerated levomethadone metabolism induced by additional misuse of benzodiazepines, barbiturates and opiates resulted in significantly lower plasma levels of the substitute. In particular, high γ‐glutamyltransferase activity was related to benzodiazepine consumption. On the other hand, an impaired liver function reflected by increased β‐globulins resulted in an insufficient body clearance and drug accumulation. Major side effects, such as sweating, were not related to plasma levels whereas withdrawal symptoms like diarrhoea or “feeling cold” correlate with lower plasma concentrations. It is concluded that polydrug misuse in the methadone maintenance therapy creates a vicious circle of enzyme induction, thus increasing “instrumental drug utilization”. However, underestimated maintenance dosage may lead to additional drug consumption resulting, finally, in therapeutic failure.