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Sodium valproate at a concentration of 300 mumol/l in whole blood, partitioned between the red blood cell and plasma to produce a red blood cell/plasma partition ratio of 0.20. Red blood cell uptake was proportional to percent free drug in plasma and uptake was maximal when plasma was replaced by buffer, producing a red blood cell/buffer ratio of 0.87. Reduction of plasma protein binding by plasma dilution, by increasing the total sodium valproate plasma concentration, or by renal or hepatic disease in 24 patients, caused a predictable rise in red blood cell uptake of drug. The red blood cell represented a relatively small compartment for free sodium valproate in blood, however uptake of the drug into this compartment increased considerably in states of reduced plasma protein binding. Because the concentration of drug in the red blood cell reflects free drug concentration in plasma, the red blood cell may serve as an indicator of free drug changes in blood.

The dissolution behaviour of four commercial and two experimental formulations of frusemide tablets has been investigated using the USP rotating basket apparatus and pH 5.0 buffer at 37 degrees C as the test medium. There is a linear relationship between the percentage dissolution in 30 min and the bioavailability relative to an oral solution of frusemide over the bioavailability range 76-97%. Predicted bioavailabilities differed by no more than 2% from the measured values.

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