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 20mg, codeine phosphate 60mg or placebo were administered in the morning. Each treatment was separated by a washout period of at least 72h. Ventilatory responses to carbon dioxide and mouth occlusion pressure, measured 1h before and at 1 and 3h after doses, were not significantly affected by either zolpidem dose; however, codeine phosphate produced a small but significant respiratory suppressant effect at 3h. Mean inspiratory flow was noninvasively assessed using respiratory inductive plethysmography 1h predose and at 1 to 5h postdose. No significant change in mean inspiratory flow was noted after zolpidem 10mg. Two hours after administration of zolpidem 20mg, 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 10mg and in 5 after 20mg of zolpidem), dizziness (in 4 after both 10mg and 20mg of zolpidem) and diplopia/blurred vision (in 4 after 20mg of zolpidem). Zolpidem appears to be well tolerated, with no respiratory suppression up to doses of 10mg and minimal suppression of mean inspiratory drive at doses of 20mg.