Summary
The pharmacokinetic parameters of the new 1.4-benzodiazepine metaclazepam (Talis®) were investigated. In particular, the question of whether the drug and/or its main metabolite accumulates in the body under steady-state conditions was studied. Two dosage regimens were compared by a randomized two-way crossover design: a once-a-day dosing (15 mg metaclazepam in the evening, = A) versus a twice-a-day dosing (5 mg in the morning plus 10 mg in the evening, = B) over ten days in twelve healthy male volunteers. Plasma levels of metaclazepam and its major biotransformation product, N-desmethylmetaclazepam, were determined. Comparing the treatments, significant differences were found for Cmax, but not for AUC-3 and Tmax. These results are also valid for the comparison of days 1 and 10 of each treatment. Higher Cmax values for dosage regimen A were found but Tmax and Cl/F remained stable in both treatments taking into account that 12 hours after the first medication, another dosing took place in treatment B. Eight hours after application, plasma levels were markedly low, Cmax values after single-dosing were nearly twice as high as after multiple dosing. Therefore based on these pharmacokinetic findings, a second dosing seems to be necessary ; the clinical relevance needs further investigation. It has been reported, in fact, that it is in general very difficult to demonstrate a correlation between blood levels and therapeutic effects for 1.4-benzodiazepines (1,2).
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References
Pöldinger W. and Wider F. (1983): Klinische Pharmakologie und Pharmakokinetik der Tranquilizer und Hypnotika,In: Langer G./Heimann H. (eds) Psychopharmaka, Grundlagen und Therapie, p. 328, Springer-Verlag, Wien.
Lader M. (1979): Correlation of plasma concentrations of benzodiazepines with clinical effects,In: Priest R.G., Pletscher A., Ward J. (eds) Sleep Research, Falcon House MTP Press.
Kali-Chemie Pharma GmbH, D-3000 Hannover (1984): Investigators broschure Talis ®
Knüchel M., Ochs H.R. (1984): Die neueren Benzodiazepine und ihre pharmakokinetischen Eigenschaften. Med. Welt35, 74–80.
Borchers F., Achtert G., Hausleiter H.J. and Zeugner H. (1984): Metabolism and Pharmacokinetics of Metaclazepam (Talis ®; Part 3: Determination of the chemical structure of metabolites in dogs, rabbits and men. Europ. J. Drug Metab. Pharmacokin.9, 325–346.
Ruhland M., Hell I., Muesch H.R. and Rohte O. (1982): Abstracts of the 13th C.I.N.P. — Congress, Jerusalem, Israel, p. 632.
Usdin E., Skolnick P., Tallmann Gr.J.F., Greenblatt D. and Paul S.M. (1983): Pharmacology of Benzodiazepines. Verlag Chemie, Weinheim/Deerfield Beach, Florida, Basel.
Molz K.H., Gielsdorf W., Rasper J., Jaeger H., Hausleiter H.J., Achtert G. and Philipp P. (1985): Comparison of the Pharmacokinetic Profile of Metaclazepam in old and young volunteers. Eur. J. Clin. Pharmacol.29, 247–249.
Madjderey A. (1979), Hippius H. (1979) and Werner J. (1981): Research Reports to be published, Kali-Chemie Pharma GmbH, D-3000 Hannover.
Rowland M. and Tozer T.N. (1980): Clinical Pharmacokinetics, Lea & Febiger, Philadelphia.
Sander A. (1984): Klinische Prüfung und Ethik-Kommission, Pharm. Ind.46, 597–600.
Modellentwicklung in der Pharmakokinetik, Special issue (1977): Arzneim. Forsch./Drug Res.27, 895–932.
Meier J., Rettig H. and Hess H. eds (1918): Biopharmazie. Theorie und Praxis der Pharmakokinetik. G. Thieme Verlag, Stuttgart/ New York.
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Gielsdorf, W., Molz, K.H., Hausleiter, H.J. et al. Pharmacokinetic profile of metaclazepam (Talis ®), a new 1.4-benzodiazepine. European Journal of Drug Metabolism and Pharmacokinetics 11, 205–210 (1986). https://doi.org/10.1007/BF03189848
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DOI: https://doi.org/10.1007/BF03189848