Biotransformation and pharmacokinetics of tetrazepam in man

The pharmacokinetics and the metabolism of tetrazepam (Musaril) were studied in 12 healthy volunteers. Tetrazepam was given orally as a single dose of 50 mg in tablet form (commercially available formulation). Tetrazepam and nortetrazepam were measured in serum using a selective and sensitive HPLC method. Urinary metabolites were identified after acid hydrolysis and thin-layer chromatographic separation. Tetrazepam is rapidly absorbed after oral administration with a lag-time of 0.45 +/- 0.10 h and reaches a peak serum level of 0.57 +/- 0.06 mg/l at 1.92 +/- 0.19 h after administration. The drug is largely distributed in the organism with an apparent volume of distribution of 225 +/- 40 l. The substitution of the phenyl moiety in the 5-position by a cyclohexenyl ring results in a different metabolism when compared to other benzodiazepines. This different metabolic pathway is the reason why only very small levels of active metabolites are present in serum. Therefore it seems reasonable, at least from the pharmacokinetic point of view, to attribute pharmacologic activity of tetrazepam mainly to the parent drug. Tetrazepam is eliminated with a half-life of 14.9 +/- 4.4 h and can be classified as a benzodiazepine with medium half-life value. This medium half-life is the result of the high hepatic clearance of the drug in spite of its large distribution volume. Since in this study 6 male and 6 female volunteers were studied it was possible to compare the pharmacokinetic profile in the two groups. No significant differences were observed.