Pharmacokinetic studies of [14C]-flumecinol in humans

The pharmacokinetics of 14C-labelled 3-trifluoro-methyl-alpha-ethylbenzhydrol (flumecinol, RGH-3332, Zixoryn), a hepatic enzyme inducer, has been studied in 6 male healthy volunteers after a single oral dose of 100 mg (11.1 Mbq; 300 microCi). Flumecinol concentration in plasma was determined (0-96 h) by capillary gas-liquid chromatography. Total radioactivity was assayed by liquid scintillation counting. The peak concentration of unchanged flumecinol in the plasma (130.2 +/- 37.7 ng/ml S.D.) was detected 2.1 h after dosing. The maximum total radioactivity concentration (1414.4 +/- 158.9 ng eq./ml) was found at 2.3 h. The ratio of the plasma radioactivity level to unchanged flumecinol indicated a rapid metabolic transformation and a marked first-pass effect in man. A two-compartment open model was constructed to describe the pharmacokinetics of the drug. The unchanged drug was eliminated from plasma with a biological half-life of 20.7 +/- 1.8 h giving a total body clearance value of 100.9 +/- 33.8 l/h. The volume of distribution of flumecinol was found to be 41.4 +/- 18.4 l/kg. However, the biological half-life of total radioactivity was much longer (35.2 +/- 11.9 h) than that of the decrease of unchanged drug. The value of total body clearance (4.1 +/- 0.6 l/h) and volume of distribution (3.2 +/- 1.6 l/kg) were found to be much lower than that of unchanged flumecinol. Radioactivity excreted with urine was 78.8 +/- 5.9% and with faeces 12.0 +/- 5.3% during 120 h.