Plasma prednisolone concentrations: comparison of radioimmunoassay and competitive protein binding assay.

A comparison was made between plasma concentrations of prednisolone measured by both competitive protein binding radioassay (CPB) and radioimmunoassay (RIA) and, with each assay, using a calibration curve generated from individual subject data and from pooling the individual calibration curva data. The plasma samples were obtained from six normal adult male volunteers who were pretreated with dexamethasone to suppress endogenous hydrocortisone and who then ingested 10 mg of prednisolone. Both the standard curve data and the plasma concentrations were evaluated statistically. It was shown that the CPB method has considerably greater precision than the RIA method and could be employed in bioavailability and pharmacokinetic studies of both prednisolone and prednisone. It was also shown that corticosteroid binding globulin cross-reacts considerably less with the major metabolite of prednisolone, 20beta-dihydroprednisolone, than the particular antiserum used in the RIA.

Effect of food on the bioavailability of prednisone.

Two commercial prednisone tablets were studied which had previously been shown by Sullivan et al.5,6 to have the slowest and fastest in vitro rates of dissolution, and the slowest and fastest rise to peak plasma prednisolone concentrations in human beings. The effect of food on the adsorption of these two tablets was studied in a crossover study, which also repeated the fasting conditions used by Sullivan et al.6 Marked differences in mean prednisolone plasma concentrations during the 0- to 2-hour absorption phase were observed between the two tablets again, but food did not affect either tablet with respect to mean plasma prednisolone concentrations.

Statistical survey of "saturation analysis" calibration curve data for prednisolone, prednisone and digoxin.

An extensive survey of radioimmunoassay calibration data for prednisolone, prednisone and digoxin indicated that the common practice of preparing calibration curves with individual subject's pre-dose plasma or serum, and using this to estimate unknown concentrations for the same subject, is not supported by statistical considerations. Preparation of calibration plots from pooled data is better because this introduces less bias in estimated concentrations. Such a method also saves a great deal of time, since it is not necessary to repeat the calibration procedure each time, "unknowns" are being assayed. The data suggest that there is no optimum calibration plot for all radioimmunoassays. Rather, each antibody-drug combination should be investigated thoroughly to determine the best calibration plot for the particular combination. We found that the best calibration plots are: the logistic-logarithmic plot for prednisolone; nonlinear least squares fit to a polyexponential equation for nisolone; nonlinear least squares fit to a polyexponential equation for prednisone; and a weighted least squares regression of normalized % bound versus concentration for figoxin. The error in the radioimmunoassay is usually concentration-dependent, and, in certain regions of the standard curve, is larger than the literature indicates, since, frequently, the error has been gauged from % bound values, but should be guaged from inversely-estimated concentrations.

Comparative bioavailability of anhydrous griseofulvin and its chloroform solvate in man.

Using a crossover experimental design, the absorption profile of griseofulvin was assessed in human volunteers after oral administration of a 500 mg dose of the antifungal antibiotic as capsules of the anhydrous (nonsolvated)-and monochloroform solvate forms of the drug. The maximum body level of drug and the rate and extent of griseofulvin absorption (or bioavailability) were significantly increased after administration of the chloroform solvate as compared to that observed after administration of the nonsolvated form of the drug. The enhanced absorption of griseofulvin chloroformate correlated well with its enhanced solubility and dissolution rate at 37 degrees C in simulated intestinal fluid (20 mM sodium deoxycholate, pH 7.5). This is the first demonstration of a drug-organic solvate displaying improved gastrointestinal absorption characteristics over the anhydrous form of a drug.