In vitro-in vivo extrapolation of hepatic clearance involving active uptake: theoretical and experimental aspects.

The importance of hepatic uptake transporters in drug clearance is well recognized. The subject is reviewed with the intention of providing an overview of the concepts in order to link the increasing knowledge of transporter-mediated uptake into established models of hepatic clearance. In order to understand and quantify their impact, models of hepatic elimination that incorporate permeability barriers are required. Models that include both active and passive uptake into hepatocytes are discussed and simulations of the influence of active uptake and passive diffusion on hepatic clearance are presented. The advantages and weaknesses of a number of in vitro assays of hepatic uptake are described, and their ability to predict hepatic clearance is reviewed.

The erythrocyte sedimentation rate in the newborn period.

Determination of the erythrocyte sedimentation rate in capillary blood can be of value in identifying neonates with infection. The normal values for the method described here range from 1 mm/l hour at 12 hours of age to 17 mm/l hour at 14 days of age. Most noninfected neonates with moderate to severe RDS or with other serious illness had values well within the normal range. Infected patients had marked elevations, and the majority of values returned to normal with clinical improvement. Coombs-positive ABO hemolytic disease was also responsible for elevated values. In about half of the infected patients the rise was not seen until 24 to 48 hours after clinical symptoms first appeared. The ESR can be useful in the nursery as a preliminary step in the laboratory evaluation of the sick neonate. Serial determinations may be of aid in identifying the infected infant when the results of bacteriologic cultures are obscured by antibiotic therapy.

The effect on serum ionic magnesium of exchange transfusion with citrated as opposed to heparinized blood.

Serum Mg++ levels before, during, and after replacement transfusion were determined in 20 newborn infants. In 10 infants exchanged with acid-citrate-dextrose (ACD) blood, the level fell from 1.75 +/- 0.16 mEq./l. to 0.99 +/- 0.16 mEq./l. By contrast, levels in 10 infants exchanged with two types of heparinized blood were unchanged: the pre-exchange values were 1.59 +/- 0.11, and the postexchange levels were 1.59 +/- 0.08 mEq./l. Mean values for donor bloods were 0.42 +/- 0.07 mEq./l. with ACD blood, and 1.45 +/- 0.03 mEq./l. with heparinized blood. In vitro studies involving the addition of known amounts of citrate to standard Mg++ solutions demonstrated that the citrate caused a reduction of ionic magnesium. It is proposed that the fall in serum Mg++ when ACD blood is used for exchange transfusion is the combined result of Mg++ binding by the citrate, and the dilution effect of the relatively large proportion of anticoagulant to blood (1:3) used with the ACD mixture.