Summary
The pharmacokinetics of a single-dose acetanilide (AA) test, and the urinary D-glucaric acid output (UDGAO) were studied in healthy drug free volunteer subjects before and at the end of a fourteen-day period of medication with 5 mg diphenylhydantoin sodium (DPH) per kg metabolically active mass, thrice daily. The steady state plasma concentration (SSPC) of DPH was also determined. The SSPC of DPH was found to vary from 3.4 to 19.6 µg per ml. The mean UDGAO values increased significantly during DPH medication from 9.5 µmol per g creatinine to 29.5 (p<0.002). The half-life of plasma AA concentration decreased significantly during DPH medication from a mean of 4.2 h to a mean of 2.8 (p<0.001). However, the plasma clearance of AA did not change significantly during DPH medication. The increase of UDGAO whilst on treatment with DPH correlated positively with the SSPC of DPH. The evidence from this study suggests that measurement of UDGAO, which is a measure of the activity of the glucuronic pathway does not necessarily indicate the state of induction of oxidizing enzymes in the hepatic endoplasmic reticulum.
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Cunningham, J.L., Price Evans, D.A. Urinary D-glucaric acid excretion and acetanilide pharmacokinetics before and during diphenylhydantoin administration. Eur J Clin Pharmacol 7, 387–391 (1974). https://doi.org/10.1007/BF00558212
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DOI: https://doi.org/10.1007/BF00558212