Contrasting prevalence of delta hepatitis markers in parenteral drug abusers with and without AIDS.

Parenteral drug abusers are the second largest group at risk for developing AIDS (25% of US cases) and a major risk group for infection with both hepatitis B virus (HBV) and the HBV-dependent RNA hepatitis delta virus (HDV). This study was conducted to determine the prevalence in 1984-1985 and relationships of HDV and HBV infections in 372 unselected parenteral drug abusers without AIDS or symptoms related to human immunodeficiency virus type 1 (HIV-1) infection (but 49% of whom were positive for HIV-1 antibodies) and in 53 drug abusers hospitalized with AIDS. The prevalence of HDV markers in the combined study groups was 20%; 81% of study subjects with hepatitis B surface antigenemia (HBsAg) had one marker for HDV infection. Significant differences were found between patients with and without AIDS with respect to the prevalence of hepatitis delta antigen (5.7% vs. 0.8%, P less than .05) and antibody (0 vs. 21.4%, P less than .01) and HBsAg (15.1% vs. 5.1%, P less than .05). The significantly higher prevalence of hepatitis delta antigen and HBsAg in subjects with AIDS suggests that persistence or reactivation of these viruses is significantly greater among parenteral drug abusers with AIDS than among those without AIDS. These findings, along with the absence of hepatitis delta antibodies in the drug abusers with AIDS, are probably related to the profound general immunosuppression that occurs in AIDS.

Altered methadone pharmacokinetics in methadone-maintained pregnant women.

We studied the influence of human pregnancy on the maternal disposition and effects of methadone. Nine healthy pregnant women who had been on p.o. methadone maintenance for at least 2 months were studied between 20 and 34 weeks of gestation (phase I), 35 and 40 weeks (phase II), 1 to 4 weeks post partum (phase III) and 8 to 9 weeks post partum (phase IV). Two subjects who breast-fed their infants had plasma and breast milk samples collected simultaneously. With or without normalization for dose and body weight, trough plasma concentrations of methadone were significantly lower and total or unbound methadone clearances greater during pregnancy than after delivery. Plasma protein binding of methadone was lower during pregnancy but the difference was only statistically significant between phases I and IV. The greater ratios of urinary excretion of the major metabolites to total and unbound methadone areas under the curve during pregnancy suggests that methadone metabolism was enhanced. The ratios of concentrations of methadone in milk to plasma were constant in two subjects, 0.32 +/- 0.06 and 0.61 +/- 0.07, respectively. Some of the women reported symptoms of methadone withdrawal during pregnancy, even when the daily methadone dose did not change. Because of the lower plasma methadone concentrations, increased methadone doses may be required during pregnancy to achieve methadone maintenance.

Methadone, monoamine oxidase, and depression: opioid distribution and acute effects on enzyme activity.

Narcotic withdrawal is often accompanied by an atypical depression with responds to resumption of narcotics. We hypothesized that methadone might exert its antidepressant effects through monoamine oxidase (MAO) inhibition. The current study examined 3H-methadone distribution in rat brain and effects on regional MAO activity with acute doses (2.5 mg/kg) which approximate those found during chronic methadone maintenance in man. Limbic areas (amygdala, basomedial hypothalamus, caudate-putamen, hippocampus, preoptic nucleus), as well as pituitary and liver were assayed for MAO activity and methadone concentration. MAO activities did not differ significantly in acute methadone or saline-treated cage-mates at 1 or 24 hr. The concentrations of methadone at 1 hr ranged between 17 and 223 ng/100 mg wet wt tissue in the preoptic nucleus and pituitary, respectively. No significant correlation was found between change in MAO activity (MAO methadone/MAO saline) and methadone concentration in any region at 1 or 24 hr. This study does not support the hypothesis that methadone acts as an antidepressant through MAO inhibition, at least not following acute administration of this exogenous opioid.

Circadian rhythms and levels of beta-endorphin, ACTH, and cortisol during chronic methadone maintenance treatment in humans.

Previous studies have shown alterations of neuroendocrine function in humans receiving any narcotic on short-term basis or short-acting narcotics on a chronic basis. In this study of 16 well-stabilized patients, it was demonstrated that normalization of hypothalamic-pituitary-adrenal axis function, as reflected by normal levels and normal circadian rhythm of levels of beta-endorphin, ACTH and cortisol, is achieved during long-term steady state methadone maintenance treatment of former heroin addicts.