The urinary excretion profile of naltrexone and metabolites in man

The urinary excretion pattern of free and conjugated naltrexone and the metabolite 6 β hydroxynaltrexone was determined for six human subjects for a period of 6 days after oral administration of 50 mg of naltrexone. The levels of free and conjugated drug and metabolite were determined by a gas chromatographic analysis procedure using naloxone as an internal standard and by correlating peak height ratios to concentration. The mean excretions ± SE of free naltrexone and 6 β hydroxynaltrexone were estimated as 1.2 ± 0.2 and 26.3 ± 2.2% of administered dose, respectively. The mean excretions of conjugated naltrexone and metabolite were estimated as 9.7 and 16.4% of administered dose, respectively. The timed urinary excretion profile indicated that naltrexone is metabolized and excreted rapidly (mean excretion t 1/2 = 1.1 hr), whereas the free metabolite, 6 β hydroxynaltrexone, persists at detectable levels for 6 days (mean excretion t 1/2 = 14-18 hr). Preliminary dose ranging studies of 6 β hydroxynaltrexone in the chronic spinal dog suggest antagonistic activity of the metabolite.