A NOVEL-APPROACH FOR THE DETERMINATION OF HUMAN MILK PLASMA RATIOS - CORRELATION OF IN-VIVO AND IN-VITRO PARACETAMOL MILK/PLASMA RATIOS/

To study the transfer of drugs from plasma into human milk [milk/plasm a (M/P) ratio], we developed an in vitro method using paracetamol as t he standard. The results obtained after equilibrium dialysis between m ilk and plasma were correlated with those obtained in vivo. For the in vivo study, 8 healthy postpartum women were enrolled as volunteers on the third postpartum day. After the ingestion of paracetamol 650mg, t he in vivo comparison of milk and plasma area under the concentration- time curves (M/P(AUC)ratio) yielded a ratio of 0.94. In vitro determin ation of the M/P ratios was carried out on plasma and milk taken on th e third and 26th days after delivery. The M/P ratio obtained after equ ilibrium dialysis (0.91 +/- 0.01) was in good agreement with that foun d in vivo. A strong correlation was found between plasma and milk conc entrations obtained by both in vitro (r = 0.96, p < 0.0001) and in viv o procedures (r = 0.89, p < 0.001). These results demonstrate that the in vitro determination of M/P ratios for drugs that transfer in milk by passive diffusion, is similar to the data obtained in vivo. We conc lude that this method can be used to avoid ethical constraints associa ted with the in vivo determination of human milk and plasma relative c oncentrations.