Drug distribution in whole blood of mothers and their newborn infants

Abstract

The distribution of cloxacillin and flucloxacillin in whole blood from seven newborn infants and their mothers was determined in vitro by equilibrium dialysis at 37 degrees C. Seven healthy, non-pregnant women of reproductive age served as controls. The distribution of the penicillins to erythrocytes was the same in the infants as in the adults. It was significantly lower in the presence of plasma albumin than when plasma was replaced by isotonic phosphate buffer. The plasma protein binding of cloxacillin and flucloxacillin in 22 infants was significantly lower than in the controls, but was slightly higher than in the mothers. A significant correlation between binding of cloxacillin and flucloxacillin in the same individual suggested that the two drugs were bound to similar sites. During the first postnatal week binding in infant plasma decreased. This change was correlated with an increase in the bilirubin levels. In the mothers, the binding increased during the first week after delivery. On the basis of the distribution data, maternal to fetal plasma and whole blood concentration ratios at equilibrium were calculated. These ratios were lower for flucloxacillin (medians 0.770 and 0.821, respectively) than for cloxacillin 0.996 and 1.094). Accordingly, at equilibrium somewhat higher levels of flucloxacillin should appear on the fetal than on the maternal side, whereas the concentrations of cloxacillin would be expected to be approximately the same.

Drug Binding to Plasma Proteins During Human Pregnancy and in the Perinatal Period

“…The theoretical relationship between total plasma concentrations on both sides of the placenta may be calculated from the plasma protein bind ing values in the mother and neonate, provided that plasma water concen trations are equal [7] (eq. 2).…”

“…Two sizes of cells were used; one suitable for samples of 100 pi on each side, the other for samples of 500 pi. The technical performance of the equilibrium dialysis process has been described in detail in an earlier publication [7], The time of dialysis was 18-22 h. All samples were run in duplicate.…”

“…The fraction unbound in plasma was expressed as (l-fp). The hypothetical maternal to fetal plasma concentration ratio (Cpm/CPjf) was calculated as [7]:…”

“…In a previous study [7] of two highly bound antibiotics, cloxacillin and flucloxacillin, we found a considerable decrease in protein binding in plasma of 22 women and their infants at delivery in comparison to the binding in plasma of nonpregnant women. During the 1 st postnatal week, binding in maternal plasma almost returned to values of the nonpregnant women.…”

Pharmacokinetics of Oral Cefatrizine in Pregnant and Non-Pregnant Women with Reference to Fetal Distribution

“…The extensive CFT plasma protein binding ( 1 60%) offers a good support to this conclusion, since decreased protein binding during pregnancy will affect drug penetration into tissues, increasing the V d [15] . The penicillins cloxacillin and flucloxacillin, presenting a 90-95% plasma protein binding, are bound less in pregnant than in non-pregnant women [16] .…”