Trimethadione as a probe drug to estimate hepatic oxidizing capacity in humans.
E Tanaka, A Ishikawa, M Abei, S Kobayashi
Index: Comp. Biochem. Physiol. C, Pharmacol. Toxicol. Endocrinol. 115(3) , 211-6, (1996)
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Abstract
Trimethadione (TMO) has the properties required of probe drugs for the evaluation of hepatic drug-oxidizing capacity in humans in vivo. TMO is demethylated to dimethadione (DMO), its only metabolite, in the liver after oral administration. Involvement of two cytochrome P450's--CYP2C9 and 3A4--in TMO metabolism has been seen in humans, but involvement of 1A2 is not clearly established. In humans with various types of liver disease and hepatectomy, the serum DMO/TMO ratios, which were measured on blood samples obtained by a single collection 4 hr after oral administration of TMO, correlated well with the degree of hepatic damage. This finding suggests that TMO may be used as a probe drug in the rapid determination of the functional reserve mass of the liver as well as hepatic drug-oxidizing capacity in humans in vivo.
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