A. Darragh

Bioavailability of p-chlorophenoxyisobutyric acid (clofibrinic acid) after repeated doses of its calcium salt to humans

SummaryPlasma concentrations and bioavailability of clofibrinic acid have been estimated under conditions approaching the steady-state during a ten-day period of administration as clofibrate or as a calcium clofibrinate-carbonate combination (1:1 w/w) at a dosage interval of 12 h. Formulation — related differences in bioavailability were not significant, and the 95% confidence limits of these differences were within −2% to +8% of the mean for the reference formulation of clofibrate. The mean steadystate plasma concentrations of clofibrinic acid measured on the tenth day of dosing were 116 µg/ml±22 S.D. and 119 µg/ml±23 S.D. after administration of 885 mg as clofibrate and the calcium clofibrinate-carbonate combination respectively. The peaks of mean plasma concentrations were 70 µg/ml±15 S.D., 119 µg/ml±32 S.D. and 131 µg/ml±26 S.D. on the first, fifth and tenth day of dosing with clofibrate, and 62 µg/ml±13 S.D., 127 µg/ml±S.D. and 143 µg/ml±25 S.D. on the corresponding days of dosing with the calcium clofibrinate-carbonate combination. After the last dose on the tenth day of dosing, the mean apparent half-lives of elimination of clofibrinic acid from plasma were 24.2 h±4.4 S.D. and 25.5 h±3.2 S.D. after administration of clofibrate and the calcium clofibrinate-carbonate combination respectively.

Determination of heptaminol in human plasma and urine by high-performance liquid chromatography

Heptaminol was measured in plasma and urine following pre-column derivatisation with o-phthalaldehyde and reversed-phase high-performance liquid chromatography employing fluorescence detection. The limits of detection were sufficient for pharmacokinetic studies of the drug after clinically-used doses. Plasma concentrations of heptaminol reached peak levels (2.19 micrograms/ml) at 0.75 h after single oral doses (0.47 g of heptaminol) and declined with a half-life of 2.1 h (+/- 0.5 S.D.). Heptaminol was well absorbed and excreted rapidly, mainly unchanged in urine, 82% dose (+/- 10 S.D.).

Determination of the antispasmodic agent ethaverine in human plasma by high-performance liquid chromatography

Ethaverine can be measured in the plasma of human subjects by reversed-phase high-performance liquid chromatography employing UV detection. The limit of detection was 2 ng/ml, and the precision was +/- 14, +/- 6 and +/- 2% at concentrations of 5, 25 and 50 ng/ml respectively. A peak mean plasma drug concentration of 20 ng/ml occurred at 1.5 h after single oral doses of a capsule formulation to human subjects, and declined with a half-life of 2.9 h.

High-performance liquid chromatographic determination of the introimidazole azanidazole in human plasma and urine

Abstract Azanidazole can be measured in plasma and urine by reversed-phase high-performance liquid chromatography employing UV detection. Peak mean plasma concentrations of azanidazole, of 267 ng/m., occurred at 1.5 h after single oral doses to human subjects, and declined with a half-life of 0.8 h. Less than 0.5% of the dose was excreted in the urine as unchanged drug. Metabolites of azanidazole were also detected by the procedures used.