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A method of isolating a single polypeptide from human plasma, termed peptide H for its histaminopexic or histamine-binding capability, is described. The peptide was obtained by acid precrystallization of human plasma, followed by water extraction of the precipitate and separation on an ion-exchange column. A molecular weight of 4492 was calculated from amino acid analysis. A dynamic dialysis technique was used to study the binding of histamine to peptide H. No binding of histamine to peptide H was observed in the absence of Ca+2; however, in the presence of Ca+2, binding of histamine to peptide H did occur. It was determined that histamine first forms a complex with Ca+2, with subsequent binding of the Ca+2-histamine complex to peptide H. From the dialysis data and kinetic analysis, it was possible to demonstrate that the data are consistent with a peptide having three binding sites for the Ca+2-histamine complex, two fast sites and one slow site.

The adhesion of a polymer film to selected tablet substrates was studied. The effect of tablet surface roughness and film‐coating solvent on the adhesion of the film to the tablet was determined. A film‐coating solvent having a solubility parameter close to that of the polymer was found to produce a stronger adhesional bond than a solvent having a lower surface tension. An increase in tablet surface roughness also increased film adhesion to the tablet. The adhesion was measured as the force required to peel a section of film from the tablet with a stress‐strain analyzer.

The association constants of histamine with Mg2+, Ca2+, Sr2+, and Ba2+were determined in buffer solutions at constant pH using an ion selective electrode. These cations enabled histamine to bind to peptide H. A minimum cation binding concentration was required for histamine binding. A linear relationship existed between the minimum cation binding concentration and the log of the equilibrium constant for the histamine–cation complexes, indicating that the specificity of the alkaline earth cations in promoting histamine binding was due to the difference in their ability to complex with histamine. The monovalent cations, Na+, K+, and Cs+, inhibited histamine binding to peptide H, with the extent of inhibition dependent on cation concentration. An ion-exchange mechanism or a conformation change in the peptide may ac-count for the inhibition.

The use of pharmacological responses such as pupil diameter for dosage individualization, bioavailability, and pharmacokinetic analyses is becoming more widespread. Attempts to use pupil diameter to assess morphine bioavailability illuminate the fact that multiple responses, nonlinearities, and the condition of the subject can produce misleading results unless the applicability of the method is confirmed.

The diffusion of acetazolamide from buffered saline and buffered albumin solutions into human erythrocytes has been characterized. A model was developed for describing the effects of both intra- and extracellular binding on the approach to distributional equilibrium. Unbound acetazolamide entered the cells via an apparent first-order process at a rate that was unaffected by salicylate at a therapeutic concentration of 200 μg/mL. Salicylate concentrations ranging from ~100 to 400 μg/mL were, however, extremely effective in displacing acetazolamide from its serum protein binding sites. Free fractions of acetazolamide in human serum were found to increase by an order of magnitude as salicylate concentrations approached 400 μg/mL, thereby greatly increasing the concentration of unbound drug available for passive diffusion into cells. The results indicate that while competitive binding effects, which may alter unbound drug concentration–time profiles and potentially impact on toxicity, do occur, alterations in red cell membrane permeability, which could adversely affect carbon dioxide transport, are not of significance.

A mathematical analysis of solute flow in a descending column following dissolution is presented. The acceleration of a solute particle from zero velocity, when it is in the solid phase, to its final equilibrium descending velocity was analyzed. The maximum velocity for N-(3-methylphenyl)acetamide developed essentially at the solidliquid interface, contradicting the postulate of a microsize diffusional layer. The possibility of a diffusional layer existing for solids of lower solubility than N-(3-methylphenyl)acetamide is discussed.