The in vivo and in vitro studies of drug milk: Plasma distribution and assessing the risk to infant

Abstract

Postpartum depression occurs in approximately 10 percent of women who give birth and is associated with substantial morbidity in mothers and their children. For some women, treatment with an antidepressant drug may be necessary but complicated by their desire to continue to breast-feed.In vitro studies were carried out to study the different factors that may affect the diffusion of drugs to milk. The protein binding of drugs in plasma, albumin, skim milk, whey and casein was studied by ultrafiltration. In-vitro M/P ratio was determined experimentally by equilibrium dialysis. It was found that fraction of unbound drugs were higher at a lower protein concentration and pH. The M/P ratio indicated the more drugs will transfer to milk at lower milk pH. The bupropion was found to be degradable when conducting dialysis study. For this, the degradation studies were carried out in different biological mediums. It was found that bupropion degraded rapid under 37a??. Its degradation followed first-order rates, fitting Arrhenius kinetics. And it is sensitive to basic environment than to acidic condition.In vivo studies were conducted using lactation rabbit to evaluate the M:P ratio in different lactation stages. The M:P ratio determined in colostrum period was about 6 times higher than that in mature stage. This may due to the increase of pH from colostrum to mature period. Furthermore, the in vitro and in vivo data was correlated to predict the effect of lactation period on the milk to plasma ratio and infant exposure.