Effects of zolpidem, codeine phosphate and placebo on respiration. A double-blind, crossover study in volunteers

The effects of zolpidem, codeine phosphate and placebo on respiration were evaluated in a double-blind, randomised, crossover study involving 12 healthy men. Single oral doses of zolpidem 10 or 20 mg, codeine phosphate 60 mg or placebo were administered in the morning. Each treatment was separated by a washout period of at least 72 h. Ventilatory responses to carbon dioxide and mouth occlusion pressure, measured 1 h before and at 1 and 3 h after doses, were not significantly affected by either zolpidem dose; however, codeine phosphate produced a small but significant respiratory suppressant effect at 3 h. Mean inspiratory flow was noninvasively assessed using respiratory inductive plethysmography 1 h predose and at 1 to 5 h postdose. No significant change in mean inspiratory flow was noted after zolpidem 10 mg. Two hours after administration of zolpidem 20 mg, mean inspiratory flow was significantly lower than after placebo, possibly related to some individuals falling asleep during data collection. All volunteers reported adverse events; the most common were slurred speech (in 1 after 10 mg and in 5 after 20 mg of zolpidem), dizziness (in 4 after both 10 mg and 20 mg of zolpidem) and diplopia/blurred vision (in 4 after 20 mg of zolpidem). Zolpidem appears to be well tolerated, with no respiratory suppression up to doses of 10 mg and minimal suppression of mean inspiratory drive at doses of 20 mg.