Distribution of indomethacin in human milk and estimation of its milk to plasma ratio in vitro |
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| Authors: | Beaulac-Baillargeon L Allard G |
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| Affiliation: | Research Center, St-François d''Assise Hospital, School of Pharmacy, Laval University, Ste-Foy, Québec, Canada. |
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| Abstract: | 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. |
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