The reduction of the number of animals used in the biological assay of insulin.

The biological control of insulin is vital as it is administered daily to a large proportion of the population during the major part of their lives. The development of the biological assay of insulin will be described with the progressive evolution of methods eventually to dispense with the need for animals. From the quantal Mouse Convulsion Method using around 600 mice per sample to the quantitative Mouse Blood Glucose method using an average of 120 mice per sample in which the fall in the blood glucose levels is used to estimate the potency of insulin by its hypoglycaemic effect. This was followed by the development of the in vitro Radioreceptor Method which is a procedure based on competition between the binding of insulin and [125I]-insulin to cells of the cultured human IM-9 cell line. The production of highly purified insulin by the Pharmaceutical Industry has made possible the recent introduction of new High Performance Liquid Chromatography technology.

Influence of soft gelatin on digoxin absorption.

1 The influence of encapsulation in soft gelatin on the absorption of digoxin from a solvent mixture of polyethylene glycol 400 90% W/W, ethanol 6% W/W, propylene glycol 3% W/W and water 1% W/W was studied in eight healthy volunteers. 2 Each volunteer received 0.6 mg digoxin as solution alone, as three intact capsules containing digoxin solution, as three capsules containing digoxin solution sectioned in half and as three capsules containing digoxin solution dissolved in water prior to administration. 3 There was no significant difference between the four treatments in terms of area under the plasma concentration--time curves for 7 h, peak plasma concentrations, time to peak or in the cumulative urinary excretion for 6 days. 4 It is suggested that a constituent of the solvent rather than the presence of or encapsulation within soft gelatin may be the determining factor in enhanced absorption of digoxin from soft gelatin capsules as compared to aqueous solution or tablets of rapid dissolution rate.

Effect of a standard breakfast on digoxin absorption in normal subjects.

The influence of food on absorption of digoxin was studied in 6 healthy volunteers who received 1.0 mg digoxin as 4 tablets of Lanoxin either after an overnight fast, immediately after a standard breakfast, or 90 min after a standard breakfast. There was no significant difference between the three regimens in terms of area under the plasma concentration-time curve for 79 hr or in the 10-day cumulative urinary excretion. The mean peak plasma concentration was higher (p less than 0.05) when digoxin was given fasting (4.2 +/- 0.46 ng/ml) than immediately after food (2.8 +/- 0.24 ng/ml). The mean peak plasma concentration when digoxin was administered 90 min after food (3.3 +/- 0.30 ng/ml) was intermediate but not significantly different from either of the other mean peak concentrations. The results demonstrate that ingestion of food decreases rate but not extent of absorption of concurrently administered digoxin.

A completely absorbed oral preparation of digoxin.

Digoxin absorption was studied in healthy volunteers by determination of peak plasma concentrations, areas under plasma concentration curves, and urinary excretion after single-dose administration. By comparison with an aqueous solution, increased rate and extent of absorption occurred from experimental soft gelatin formulations of digoxin in solution. Enhanced bioavailability of the capsules was not affected by altered volume of contained solvent. Digoxin was considerably better absorbed from capsules than from tablets of moderately high dissolution rate. Mean percentage intestinal absorption was 75% from tablet and 97% from capsules. Reduced between-subject variability accompanied the enhanced absorption from capsules.