A subject’s death at Johns Hopkins, after inhalation of hexamethonium, led to the FDA discouraging further human research involving inhalation of non-approved medications/drugs. This report describes the safety of inhalation studies using pharmaceutical grade capsaicin and looks at the results of high pressure liquid chromatography (HPLC) analyses of administered doses compared to their calculated concentrations.
35 normal male subjects underwent capsaicin inhalation challenges under an Investigational New Drug (IND) protocol approved by the FDA. Study protocol included the use of pharmaceutical grade capsaicin (Formosa Laboratories, Taiwan), subject safety procedures, and preparation of capsaicin doses by a registered pharmacist. Serial measurements of spirometry and impulse oscillemetry were recorded as well as HPLC measurements of administered capsaicin doses. Continuous electrocardiography, blood pressure, and oxygen saturation were monitored.
There were no adverse reactions at any dose tested, including the highest capsaicin concentration of 1000 micromoles. Spirometry and oscillemetry did not change. HPLC measurements of the administered capsaicin concentrations were significantly lower than the calculated doses. The solutions averaged 14.7% lower than the calculated values (2.2% lower at the highest dose of 1000 micromoles and 28.1% lower at the lowest dose of 0.48 micromoles). Coefficient of variation for the doses ranged between 1.7% (125 umol) and 5.4% (0.49 umol). There was stability of prepared capsaicin doses up to 4 months.
Performance of capsaicin challenges can be considered safe for normal individuals when using pharmaceutical grade capsaicin and following strict safety procedures. HPLC documents accurate capsaicin concentrations for inhalation studies. The actual administered doses are lower than calculated, and HPLC analysis improves accuracy and reproducibility and insures the safety of subject volunteers.
Performance of capsaicin challenges can be considered safe, but there is a discrepancy between calculated and actual dosages administered. This brings in to question the accuracy and reproducibility of previously reported data.
D Sams, None.