DOSE PROPORTIONALITY AND PHARMACOKINETICS OF ORAL TRANSMUCOSAL FENTANYL CITRATE

Background: The pharmacokinetics of a single dose (15 mu g/kg) of oral transmucosal fentanyl citrate (OTFC) have been characterized. A range of doses may eventually be used in clinical practice. The goal of thi s study was to determine if the pharmacokinetics of OTFC are dose prop ortional for doses ranging from 200 to 1,600 mu g. Methods: Twelve hea lthy male volunteers mere studied on four different occasions, receivi ng 200, 400, 800, and 1,600 mu g OTFC in a double-blind, randomized pr otocol Venous blood samples were collected at selected times during an d after dosing for a 24-h period and assayed for fentanyl using a radi oimmunoassay. Maximum concentration, time to maximum concentration, ar ea under the curve, and elimination half-life mere determined for each dose administered. In addition, respiratory rate, need for verbal pro mpting to breathe, and supplemental oxygen requirements were noted. Re sults: Mean fentanyl concentration time curves were similarly shaped w ith increasing doses. Both peak concentrations and area under the curv e increased linearly with an increase in dose, whereas time to reach p eak serum concentrations did not vary significantly between doses. Exc ept for the 200-mu g dose, the apparent elimination half-life remained relatively constant (358-386 min). The incidence of low respiratory r ate, supplemental oxygen requirement, and number of breathing prompts significantly increased with increasing doses. Conclusions: Oral trans mucosal fentanyl citrate exhibits dose-proportional pharmacokinetics o ver the dose range of 200-1,600 mu g.