Trimethadione as a probe drug to estimate hepatic oxidizing capacity in humans.
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.
Tanaka
E
E
Institute of Community Medicine, University of Tsukuba, Ibaraki-ken, Japan.
Ishikawa
A
A
Abei
M
M
Kobayashi
S
S
D000284:Administration, Oral; D000818:Animals; D002986:Clinical Trials as Topic; D004114:Dimethadione / Q000097:blood*; D006801:Humans; D008107:Liver Diseases / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D016877:Oxidants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014293:Trimethadione / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D016877:Oxidants; D004114:Dimethadione; D014293:Trimethadione