DISTRIBUTION OF INDOMETHACIN IN HUMAN-MILK AND ESTIMATION OF ITS MILKTO PLASMA RATIO IN-VITRO

1 The distribution of indomethacin in fat and protein fractions of col ostrum and mature milk as well as its milk to plasma drug concentratio n ratio (M/P ratio) were determined in vitro. 2 The extent of plasma p rotein binding of indomethacin (5-20 mug ml-1) was greater-than-or-equ al-to 99.6%. The protein binding of indomethacin in colostrum was 46.0 % at pH 7.4. The lower protein content of mature milk compared with co lostrum was associated with a significant decrease in the extent of dr ug protein binding (46 +/- 1.93 to 35 +/- 1.0 s.e. mean). Protein bind ing was also decreased significantly in 8% fat mature milk (20.3 +/- 2 .4 s.e mean) but was constant over the pH range 7.4 to 6.8. 3 About 40 % of indomethacin added to milk was associated with the fatty layer. T he indomethacin M/P ratio determined by equilibrium dialysis was less than 0.01. Hence the maximum infant daily dose was estimated to be 0.0 06 mg kg-1. 4 Our results indicate that indomethacin transfers to milk by simple diffusion according to its physicochemical properties, and that treatment with indomethacin is not a contraindication to breast f eeding.