Inhibition of cough-reflex sensitivity by benzonatate and guaifenesin in acute viral cough

Acute cough due to viral upper respiratory tract infection (URI) is the most common form of cough and accounts for tremendous expenditure on prescription and non-prescription cough products worldwide. However, few agents have been shown in properly conducted clinical trials to be effective for cough due to URI. The present study evaluated the effect of benzonatate 200 mg (B), guaifenesin 600 mg (G), their combination (B + G), and placebo (P) on capsaicin-induced cough in 30 adult nonsmokers with acute URI. On 3 separate days within a 7-day period, 1 h after ingesting randomly assigned study drug in a double-blind fashion, subjects underwent capsaicin cough challenge testing, which involved inhalation of incremental doubling concentrations of capsaicin until the concentration of capsaicin inducing 5 or more coughs (C₅) was attained. Each subject received 3 of 4 possible study drugs. G (p = 0.01) but not B (p = NS) inhibited cough-reflex sensitivity (log C₅) relative to P. The combination of B + G suppressed capsaicin-induced cough to a greater degree than B alone (p < 0.001) or G alone (p = 0.008). The mechanism by which the combination of B + G causes a potentiation of antitussive effect remains to be elucidated. Our results suggest that B + G may be an effective therapy for acute cough due to the common cold (URI).