Correlation of the nalorphine test with concentration of metabolites of codeine in the urine after single doses and continuous administration of codeine

Single doses of codeine cause miosis which is not reversed by nalorphine, as the miosis with other morphinelike drugs is. When codeine was given four times a day, most subjects gave positive nalorphine (pupil) tests on the third day. Urinalysis for codeine and its metabolite morphine revealed that subjects with the highest urine drug levels had the most strongly positive pupil tests, but the gradual development of a positive pupil test was not related to increasing concentrations of morphine in the urine. When codeine was infused continuously (30 mg. per hour) to produce “acute tolerance,” the pupil test was positive in 8 hours. In the dog, a species which forms norcodeine but not morphine from codeine, the pupil test was negative after a single injection of codeine but became positive after 2 to 3 days of intermittent injections. The data suggest that positive nalorphine tests occur only in subjects tolerant to codeine.