A pharmacokinetic study of sublingual aerosolized morphine in healthy volunteers.

A pharmacokinetic study was undertaken to compare the pharmacokinetics of morphine after an intravenous dose with the pharmacokinetics after a sublingual dose administered from an aerosol. Plasma levels of morphine, morphine-3-glucuronide and morphine-6-glucuronide were measured in five normal volunteers after morphine administration by the intravenous route and from a novel sublingual pressurized aerosol formulation. The mean (+/- s.d.) bioavailability of the sublingual aerosol morphine was 19.7 +/- 6.7%. The morphine-3-glucuronide/morphine and the morphine-6-glucuronide/morphine ratios were 5.1 +/- 1.6 and 1.2 +/- 0.4, respectively, for the intravenous route and 28.3 +/- 11.3 and 5.2 +/- 1.4, respectively, for the sublingual route. The combined total areas under the plots of systemic concentration against time (AUC) for the metabolites after the two routes was not significantly different. When compared with published data for oral administration the results demonstrate that the sublingual aerosol morphine might provide an alternative to conventional methods of morphine delivery, and has similar pharmacokinetics to a sublingual morphine tablet. It has no particular pharmacokinetic advantages over oral morphine, except a potential for a faster onset of analgesia. Bioavailability, maximum plasma concentration, Cpmax, and the time at which the maximum plasma concentration is reached, Tmax, are equivalent to those for orally administered morphine.