PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTIONS IN AN OUTPATIENT MAINTENANCE THERAPY OF INTRAVENOUS HEROIN USERS WITH LEVOMETHADONE

The plasma levels of 42 patients on a levomethadone maintenance treatm ent programme for intravenous heroin users were measured before and, r espectively, 1, 2 or 4 hours after oral routine administration and rel ated to the individual additional drug usage (detected by urine drug s creening), liver function, side-effects and withdrawal symptoms. In ge neral, accelerated levomethadone metabolism induced by additional misu se of benzodiazepines, barbiturates and opiates resulted in significan tly lower plasma levels of the substitute. In particular, high gamma-g lutamyltransferase activity was related to benzodiazepine consumption. On the other hand, an impaired liver function reflected by increased beta-globulins resulted in an insufficient body clearance and drug acc umulation Major side effects, such as sweating, were not related to pl asma levels whereas withdrawal symptoms like diarrhoea or ''feeling co ld'' 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 utili zation''. However, underestimated maintenance dosage may lead to addit ional drug consumption resulting, finally, in therapeutic failure.