Initial pharmacokinetic, safety and efficacy evaluation of nasa morphine gluconate for breakthrough pain in cancer patients

Patients with controlled background pain associated with cancer frequently also experience episodes of moderate to severe intensity breakthrough pain. Opioid pharmacotherapy, particularly with oral morphine, remains the cornerstone for the management of cancer pain. Nasal administration of opioids provides a mechanism for more rapid drug absorption and more rapid onset of pain relief compared with oral dosing. This non-randomized, open-label, uncontrolled investigation evaluated the pharmacokinetics, safety and efficacy of a single 40 mg dose of nasal morphine gluconate, administered to cancer patients in response to an episode of breakthrough pain. Single dose nasal morphine aluconate administered to 11 patients was associated with effective plasma morphine concentrations (mean C-max 64 ng/ml; range 33.8-121 ng/ml) and low plasma morphine metabolites (morphine-6-glucuronide mean C-max 114 ng/ml; range 46-189 ng/ml; morphine-3-glucuronide mean C-max 572 ng/ml; range 257-990 ng/ml). Side effects were minor and limited to nasal irritation. Patients reported rapid onset of pain relief (perceptible pain relief achieved in 10/11 patients, time to onset 2.4 +/- 2.1 min; and meaningful pain relief, achieved in five patients. 6.8+/- 7.3 min to onset, mean t(max) 0.36 h). Pain intensity scores were significantly reduced at all times after dosing; pain relief scores were unchanged. Patient satisfaction ratings were high. These results show that nasal morphine has rapid absorption and apparent onset of effect. Additional multi-dose, dose-ranging and placebo-controlled studies of nasal morphine for cancer pain are warranted. (C) 2003 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.