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

Summary

Plasma 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.