Reduction of Hepatic Drug Metabolizing Capacity in the Elderly: Trimethadione and Antipyrine as Model Drugs for Estimation of Metabolizing Capacity

Abstract

The serum concentration ratios of dimethadione (DMO) /trimethadione (TMO) after 4 mg/kg TMO administration and urinary excretion of antipyrine metabolites, norantipyrine (NORA), 4-hydroxyantipyrine (OHA) and 3-hydroxymethylantipyrine (HMA) after 7mg/kg antipyrine administration were studied in elderly patients and in young healthy volunteers as controls.
Serum TMO concentrations were shown to be significantly higher in the elderly than those in the controls, and DMO concentrations in the elderly were significantly lower than those in the controls. The serum DMO/TMO ratios in the elderly were decreased to 39-52% of those of the controls up to 6 hr after TMO administration.
The 48 hr urinary excretion of NORA and OHA were decreased to approximately 60% of the control values and HMA was increased to 142%.
The results indicate that the activities of the isozymes of cytochrome P-450, which are responsible for N-demethylation such as TMO to DMO, or antipyrine to NORA, are selectively decreased in the elderly.