Pharmacokinetic Characterization of a Prototype Mini Nicotine Lozenge.

Introduction: Cigarette smoking remains a substantial public health problem. Nicotine replacement therapy (NRT) is an effective treatment that increases the success of a quit attempt. There are different NRT formats with no difference in efficacy, but their pharmaceutical form or route of administration may translate into individual preferences. A novel prototype mini lozenge was developed to offer smokers a new NRT option to aid in their quit attempt. Two studies were conducted to characterize the pharmacokinetic parameters and to evaluate its bioequivalence to a commercially available nicotine mini lozenge.

Methods: Two randomized, open-label, crossover studies were conducted to evaluate either the 2 or 4 mg dose level. Heavy smokers in otherwise good health were randomly assigned to one of two treatment sequences: the prototype mini lozenge followed by a commercially available mini lozenge, or the converse. After a 5 to 7 day washout period, subjects crossed over to receive the other study treatment. Blood sampling occurred pre- and post-dose nicotine and was assessed using a validated solid-phase extraction with ultra-high-performance liquid chromatography and tandem mass spectrometry. The primary endpoint was bioequivalence as determined by maximal plasma nicotine concentration (C) and the extent of nicotine absorption (AUC and AUC). The secondary endpoints included the time to C (T), half-life, the elimination constant (K), and safety.

Results: The prototype mini lozenge was bioequivalent to the commercially available mini lozenge, with no significant difference in C, AUC, or AUC or any of the secondary outcomes. The most common treatment-emergent adverse event was throat irritation, of which all cases were mild in severity. There were no serious adverse events.

Conclusion: The prototype mini lozenge is bioequivalent to a commercially available mini lozenge and may provide smokers with a new oral NRT option to aid in smoking cessation and of tobacco dependence through the relief of nicotine withdrawal symptoms, including cravings.