The effect of hematin on the development of microsomal enzyme induction and physical dependence in mice following repeated oral propoxyphene administration

Abstract Male ICR mice (25–30 g) were pretreated with bovine hematin (20, 40 or 50 μmoles per kg per day, i.p.) for three days. During the next six-day period, animals received either 50 mg per kg per day propoxyphene-HCl or saline, p.o., in addition to the daily hematin injections. Only the highest hematin regimen depressed the induction of propoxyphene- N -demethylase activity significantly in the drug-treated animals. A similar depression below control levels was noted in the animals receiving only saline (p.o.) and hematin (i.p.). While hematin treatment abolished the metabolic tolerance to propoxyphene analgesia, such treatment failed to generate any appreciable degree of physical dependence to propoxyphene as assessed by a challenge with naloxone. These findings may be helpful in assessing the risk factors associated with the widespread use of propoxyphene.