AIMSTo investigate the possibility of a dose-response relationship for the use of domperidone in treating insufficient milk supply in mothers of preterm infants, and to quantify the exposure of the breastfed infant to domperidone.METHODSSix preterm mothers received domperidone (30 mg daily or 60 mg daily) in a double-blind, randomized, crossover trial. Milk production and serum prolactin were measured before and during the trial, and domperidone concentration in milk was measured during drug treatment.RESULTSFor milk production, two of the mothers were 'nonresponders', whereas the other four were 'responders' and showed a significant increase in milk production from 8.7 +/- 3.1 g h(-1) in the run-in phase (mean +/- SEM), 23.6 +/- 3.9 g h(-1) for the 30-mg dose (P = 0.0217) and 29.4 +/- 6.6 g h(-1) for the 60-mg dose (P = 0.0047). In all participants, serum prolactin was significantly increased for both doses, but the response was not dose dependent. Median (interquartile range) domperidone concentrations in milk over a dose interval at steady-state were 0.28 mu g l(-1) (0.24-0.43) and 0.49 mu g l(-1) (0.33-0.72) for the 30-mg and 60-mg doses, respectively. The mean relative infant dose was 0.012% at 30 mg daily and 0.009% at 60 mg daily.CONCLUSIONIn one-third of mothers, domperidone did not increase milk production. In the remainder, milk production increased at both domperidone doses, and there was a trend for a dose-response relationship. The amount of domperidone that transfers into milk was extremely low, and infant exposure via breastfeeding was not considered to be significant.