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K Minagawa

Publications and source records attributed to K Minagawa.

At least 55 records · Page 3Linked to original sources

Pharmacokinetics of rectal diazepam in the prevention of recurrent febrile convulsions.

To determine the optimum dosage schedule for intermittent rectal diazepam in suppository form for the prevention of recurrent febrile convulsions, we studied the pharmacokinetics of diazepam administered in repeated rectal doses. The plasma concentration-time data for diazepam on twice repeated rectal dosing with 0.5 mg/kg at 8-hour intervals in six infants showed that therapeutic plasma levels could be attained within 30 minutes and maintained for the first 24 hours. Most of the observed plasma diazepam levels were found to be within +/- one standard deviation of the values calculated from the pharmacokinetic parameters in six other infants with single rectal dosing. Computer-simulated plasma level profile suggested that plasma diazepam levels may reach the toxic range after administration of five or more doses. Twice repeated rectal dosing with 0.5 mg/kg of diazepam in suppository form at 8-hour intervals during the febrile period may be a rational approach for the prevention of recurrent febrile convulsions.

Diazepam↗

Determination of dexamethasone in human plasma and urine by electron-impact mass spectrometry.

A gas chromatographic-electron-impact mass spectrometric method for the determination of dexamethasone in biological fluids has been developed. Quantitation by isotopedilution mass spectrometry was carried out by selected-ion monitoring on the molecular ions of the tetra(trimethylsilyl) derivative of dexamethasone and of dexamethasone M+9 (m/z 680 and 689, respectively). The sensitivity, specificity, precision and accuracy of the method were demonstrated to be satisfactory for application to pharmacokinetic and bioavailability studies of dexamethasone after administration of a therapeutic dose.

Adult↗

Efficient chromatographic fractionation of steroids in human serum through regulation of liquid--liquid distribution ratios.

To improve the clean-up process in the analysis of biological fluid constituents, an efficient liquid--liquid distribution system was developed. Closed-bed columns containing fine diatomaceous earth granules were prepared by slurry packing for the fractionation of steroid hormones in human serum before quantitative assay by liquid chromatography or radioimmunoassay. Four columns were connected to construct the aqueous liquid--liquid chromatography--fractionation system. The first was coated with neutral water for distribution of serum, the second was weakly alkaline with sodium hydrogen carbonate for extrusion of strong acidic components, and the third was strongly alkaline with sodium hydroxide to capture oestrogens. The final column was acidic with sulphuric acid to remove basic components. Optimization of the stepwise gradient solvents was achieved on the basis of the results of a linear relationship between the logarithms of the capacity ratios and solvent composition determined from an analytical run. Neutral steroid hormones added to serum were eluted from the column system by a stepwise gradient elution technique to obtain first very non-polar materials, then progesterone and testosterone, and finally to extract the corticosteroids. Phenolic oestrogens were recovered from the strong alkaline column with a mobile phase solvent after the pH of the stationary phase had been adjusted with a phase transfer neutralizer. The fractional constituents were purified and enriched. This procedure was used to determine Solu-medrol, an acidic corticosteroid drug, in human serum.

Chromatography, Liquid↗