TRANSDERMAL ADMINISTRATION OF MORPHINE TO HEALTHY-SUBJECTS

1 Twelve healthy subjects received 10 mg morphine HCl delivered transd ermally from an occlusive reservoir applied to a small area of skin, p ainlessly de-epithelialised by vacuum suction. On a separate occasion, 10 mg morphine HCl was given as an i.v. infusion over 20 min. 2 Venou s blood samples were collected serially for 72 h and assayed for morph ine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) by h.p.l.c. Pupil size, salivation, and central nervous effects (nausea, fatigue, headache, feeling of heaviness and dysphoria/euphoria) were a lso measured. 3 After transdermal application morphine was absorbed by a first-order process to produce relatively constant plasma drug conc entrations over 11 h. The absolute bioavailability of transdermal morp hine was 75% (65-85%; 95% CI). The plasma concentrations of both M6G a nd M3G were lower after transdermal administration than after i.v. inf usion, and a considerable delay (of up to 1 h) was observed before the metabolites were detectable. AUC ratios for M3G and M6G relative to m orphine were similar after both modes of administration. 4 Non-analges ic effects were less pronounced at the lower plasma drug and metabolit e concentrations observed after transdermal delivery than after the i. v. infusion of morphine. 5 Transdermal administration of morphine warr ants investigation as an alternative route of morphine delivery.