Influence of dose of domperidone on the acute ventilatory response to hypoxia in humans

Abstract

We have studied the ventilatory responses to acute isocapnic hypoxia (SpO2 78.8 (SD 1.4)% for 10 min) in 10 male volunteers given three different doses of oral domperidone: placebo, domperidone tablets 10 mg, 20 mg or 30 mg every 8 h for 48 h on separate days. Neither baseline ventilation nor the acute hypoxic ventilatory response was significantly different from placebo for any of the domperidone doses. However, hypoxic responses were either increased with increments of domperidone or subjects were not sensitive. We arbitrarily divided subjects into two groups according to their hypoxic response-plasma domperidone concentration relationship. Analysis of subjects (n = 5) who demonstrated at least a 2-litre min-1 increase in ventilation per 10 ng ml-1 increase in plasma domperidone concentration showed the greatest augmentation of hypoxic responses with the 20-mg dose (median 19.45 (range 13.37, 22.30) litre min-1) compared with placebo (median 8.21 (3.74, 9.47)) (P = 0.003). We were unable to predict which subjects would be sensitive to the effects of domperidone.