TRIMETHADIONE : METABOLISM AND ASSESSMENT OF HEPATIC DRUG-OXIDIZING CAPACITY

Publisher Summary This chapter discusses the metabolism and assessment of hepatic drug-oxidizing capacity using Trimethadione. Measurement of the activity of drug-metabolizing enzymes of the liver, which largely depends on cytochrome P450, is essential in evaluating the capacity of oxidative drug metabolism in liver disease. Trimethadione (TMO), an antiepileptic drug, may be a more suitable candidate for estimating hepatic drug-oxidizing activity. It is rapidly absorbed from the gastrointestinal tract, distributed into total body fluids, and is extensively N-demethylated to dimethadione (DMO) by P450-dependent monooxygenases in liver microsomes. The pharmacokinetic properties of TMO enable the determination of hepatic microsomal function with a single blood sample. The chapter discusses that the TMO may be used as a probe drug for the rapid determination of the hepatic drug-oxidizing capacity and the functional reserve mass of the liver.