Effect of enzyme induction on bioavailability of hetacillin in patients treated with anticonvulsants and chlorpromazine
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The effect of liver enzyme induction on bioavailability of hetacillin was studied in patients chronically treated with anticonvulsants or chlorpromazine. 24 chronic psychiatric patients classified according to their medication in two groups (anticonvulsants, chlorpromazine) and one group of 11 healthy volunteers, received an i.m. administration of 500 mg hetacillin. Serum levels of arnpicillin derived from hetacillin in blood samples taken 2, 4 and 6 hours after the injection were measured and the half-life of the antibiotic was determined for each group. Urinary D-glucaric acid was considered the induction index. Correlation coefficients between the induction index and pharmacokinetic parameters of hetacillin were also determined. Anticonvulsants and chlorpromazine induced the liver microsomal enzymes as demonstrated by the increased D-glucaric acid excretion (P<0.001 —P<0.05). No statistically significant differences were found in serum levels and half-life of the antibiotic. Correlation coefficients suggest that enzyme induction and hetacillin bioavailability are not significantly related.
KeywordsEnzyme induction D-glucaric acid psychiatric patients anticonvulsants chlorpromazine hetacillin arnpicillin pharmacokinetics bioavailability
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