Pharmacodynamics and pharmacokinetics of dihydroetorphine hydrochloride administered sublingually in mice and rats

The analgesia. respiratory depression and immobilization in mice and rats after dihydroetorphine hydrochloride (DHE) administered sublingually (sl) were similar to those after DHE administered subcutaneously (sc), but the effective doses of sl DHE were larger than those of sc DHE. After sl [15. 16-3H] DHE 2.36 vg/kg (1/2 analgesia ED50) for mice. K^=0.273 min-l, tl(a) = 2.54 min, tmax = 10.9 min. Cmax = 202 pg/ml, K = 0.0166 min-l. t= =41.7 min, AUCO-189min = 18.2 ng.min/ml. The elimination of [15,16-3H]DHE from the blood was conformed to the single compartment model. The relative apparent bioavailability of sl [15, 16-3H]DHE for mice was l.9.2% of sc [15, 16-3H]DHE. The effects of sl DHE were easily antagonized by nalorphine. It had been recommended to test the sublingual tablet of DHE in the terminal cancer patients with pain.