Distribution of indomethacin in human milk and estimation of its milk to plasma ratio in vitro.
1. The distribution of indomethacin in fat and protein fractions of colostrum and mature milk as well as its milk to plasma drug concentration ratio (M/P ratio) were determined in vitro. 2. The extent of plasma protein binding of indomethacin (5-20 microg ml(-1)) was > or = 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 colostrum was associated with a significant decrease in the extent of drug protein binding (46 +/- 1.93 to 35 +/- 1.0 s.e. mean). Protein binding 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. The indomethacin M/P ratio determined by equilibrium dialysis was less than 0.01. Hence the maximum infant daily dose was estimated to be 0.006 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 feeding.
Beaulac-Baillargeon
L
L
Research Center, St-François d'Assise Hospital, School of Pharmacy, Laval University, Ste-Foy, Québec, Canada.
Allard
G
G
D000328:Adult; D001942:Breast Feeding; D003126:Colostrum / Q000737:chemistry; D003956:Dialysis; D005223:Fats / Q000737:chemistry; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007213:Indomethacin / Q000097:blood / Q000378:metabolism*; D008895:Milk, Human / Q000737:chemistry*; D011485:Protein Binding
D005223:Fats; D007213:Indomethacin