Serum propoxyphene concentrations in a cohort of opiate addicts on long-term propoxyphene maintenance therapy. Evidence for drug tolerance in humans.

Propoxyphene, norpropoxyphene, and cyclic dinorpropoxyphene concentrations in the sera of eight opiate addicts were measured by gas chromatography. The addicts were enrolled in a propoxyphene maintenance program and had received 800-1600 mg of propoxyphene napsylate daily for 13-50 months. Serum propoxyphene and norpropoxyphene ranged from 127 to 1070 ng/mL and 814 to 2638 ng/mL, respectively, and their ratio ranged from 0.1 to 0.4. A roughly linear dose-to-serum-concentration relationship was found for serum propoxyphene and norpropoxyphene in the cohort. Cyclic dinorpropoxyphene was detected in three of the subjects' sera. Because tolerance to propoxyphene occurs, knowledge of prior drug exposure is necessary to determine whether an elevated propoxyphene or norpropoxyphene concentration is toxic to patients or decedents with apparent propoxyphene overdose. Serum norpropoxyphene concentration exceeds that of propoxyphene following chronic propoxyphene use. Measurable cyclic dinorpropoxyphene implies chronic propoxyphene use but its absence does not exclude chronic use.