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Laboratory Safety of Capsaicin Inhalation in Healthy Younger and Older Populations Potential Template for Inhalation Research

Stuart M Brooks, Thomas Truncale and Andrew Sams

Introduction: There are inconsistencies as to the effects of age on the human cough reflex. The investigation speaks to the Federal Drug Agency’s (FDA) trepidations for conducting inhalation experiments with non-approved medications/chemicals. The investigation addresses the accuracy of the mixing methodology and analysis of capsaicin stability during seven months of storage. Methods: There is stringent safety monitoring while conducting 12 serial (0.49-1000 uMol) single breath capsaicin inhalation challenge testing (CICT) on 20 younger and 20 older healthy research volunteers using pharmaceutical-grade capsaicin (i.e., Investigational New Drug protocol-IND 69,642). The research design and subject safety measures are recommended by the Food & Drug Agency (FDA) and approved by the Institutional Review Board (IRB). Mixing of inhaled capsaicin solutions are by a Registered Pharmacist and concentration verifications are by high performance liquid chromatography (HPLC). Potency of stored capsaicin (i.e., refrigerated and shielded from UV light) is examined over 7 months. Results: There are neither adverse reactions nor statistically significant difference in capsaicin cough parameters for older and younger volunteers at any dose of capsaicin. Physiologic monitoring by spirometry, impulse oscillometry, exhaled breath nitric oxide, electrocardiography, blood pressure, pulse and oxygen saturation measurements do not change at any dose. There are differences between the concentrations of capsaicin solutions mixed by a Registered Pharmacist and actual capsaicin determination by HPLC. The differences in capsaicin concentrations are 28.1% lower for 0.49 uMol compared to a 2.2% lesser concentration for 1000 uMol solution. During storage, capsaicin remains stable for 3-months but substantially falls by six (p<0.03) and seven (p<0.004) months, especially for the lower concentrations. Conclusion: The results of this investigation embrace the safety of serial Inhalations of dilute pharmacologic grade capsaicin aerosol among older and younger normal volunteers. Incorporating rigorous FDA recommendations, inclusion of IRB oversight and monitoring by spirometry, impulse oscillometry, exhaled breath nitric oxide, electrocardiography, blood pressure, pulse and oxygen saturation measurements document inhalation safety at any dilute capsaicin aerosol dose. However, there are lower capsaicin values determined by HPLC compared to expected capsaicin concentrations when mixed by a Registered Pharmacist or after six months of storage. The investigation champions the opinion that inhalation studies involving FDA non-approved drugs or chemicals/ medications can be safely conducted when following the appropriate safety procedures such as in this research protocol.