Blood and milk concentrations of metronidazole in mothers and infants

Abstract
To assess the amounts of [the antiprotozoal agent] metronidazole and its clearance in suckling neonates whose mothers received the drug in therapeutic doses, drug levels were measured in maternal plasma and milk and in infant plasma. Eleven mothers receiving 600 mg metronidazole daily and 4 receiving 1200 mg and their 15 infants had milk and plasma levels determined with a specific semi-micro high-pressure liquid chromatographic method. Maternal mean plasma levels were 5.0 .mu.g/ml, range 1.0-11.6 .mu.g/ml (600 mg/day) and 12.5 .mu.g/ml, range 3.7-17.9 .mu.g/ml (1200 mg/day) and corresponding infant plasma levels were 0.8 .mu.g/ml, range 0.3-1.4 .mu.g/ml and 2.4 .mu.g/ml, range 0.6-4.9 .mu.g/ml. Maternal milk/plasma ratio was 1 and baby/mother plasma ratio was 0.15, independent of dosage. The levels of metronidazole hydroxy metabolite (I) were all below those of metronidazole. Simultaneous milk and blood samples showed almost identical levels. Infant total clearance of metronidazole was calculated to be .apprx. 60% of maternal clearance by body weight and 24% by body surface, independent of dosage, while maximum infant metronidazole intake was estimated to be 3.0 mg/kg per day assuming a daily intake of 500 ml milk. Simultaneous breastfeeding and metronidazole therapy should be avoided until possible harmful long-term effects on neonates are known.