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European Journal of Clinical Pharmacology

, Volume 22, Issue 3, pp 225–228 | Cite as

Pinazepam: A precursor of N-desmethyldiazepam

  • G. M. Pacifici
  • G. F. Placidi
  • P. Fornaro
  • R. Gomeni
Originals

Summary

The plasma profile of a single oral dose of pinazepam 10 mg was studied in 6 healthy male volunteers, aged 26 to 31 years. The concentrations of the parent compound and of its metabolite in plasma were measured by gas-chromatography. The peak plasma levels of pinazepam was 36.8±5.1 ng/ml and of N-desmethyldiazepam 150±13.3 ng/ml. The plasma concentration of the metabolite become higher than that of the parent compound shortly after administration, suggesting that pinazepam acts as a prodrug.

Key words

pinazepam N-desmethyldiazepam kinetics metabolism human 

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References

  1. Allen MD, Greenblatt DJ, Harmatz JS, Shader RI (1980) Desmethyldiazepam kinetics in the elderly after oral prazepam. Clin Pharmacol Ther 28: 196–202Google Scholar
  2. Biscaldi GP, Hattab J, Montanaro N, Scoz R (1971) Quantitative polygraphic evaluation of emotional tension in the study of a new benzodiazepine. Curr Ther Res 13: 606–615Google Scholar
  3. Corni L, Palmir R, Gervasi GB, Comi V, Fossati A (1976) Cinetica ematica e prove di accumolo nell'uomo di una nuova benzodiazepina (pinazepam) dopo somministrazione orale. Clin Ter 78: 111–122Google Scholar
  4. De Lisio G, Cassano GB, Castrogiovanni P, Maggini C, Sarteschi P, Wittenborn JR (1975) Therapy in psychosomatic medicine. The influence of benzodiazepine on psychomotor and intellectual activities. Pinazepam effects on performance of normal volunteers. F Antonelli (ed), pp 183–188. Luigi Pozzi RomeGoogle Scholar
  5. Gomeni R, Gomeni C (1979) AUTOMOD: a polygraphic method for an integrated analysis of linear pharmacokinetic models comput. Biol Med 9: 39–48Google Scholar
  6. Greenblatt DJ, Shader RI (1974) Benzodiazepines in clinical practice, Raven Press, New York, p 17Google Scholar
  7. Greenblatt DJ, Shader RI (1979) Single-dose kinetics of oral prazepam. Clin Pharmacol Ther 25: 211–212Google Scholar
  8. Kaplan SA, de Silva JAF, Jack ML, Alexander K, Strojny N, Weinfeld RE, Puglisi CV, Weissman L (1972) Blood level profile in man following chronic oral administration of flurazepam hydrochloride. J Pharm Sci 62: 1932–1935Google Scholar
  9. Klotz U, Müller-Seydlitz P (1979) Altered elimination of desmethyldiazepam in the elderly. Br J Clin Pharmacol 7: 119–120Google Scholar
  10. Mahon WA, Inaba T, Stone RM (1977) Metabolism of flurazepam by the small intestine. Clin Pharmacol Ther 22: 228–233Google Scholar
  11. Mandelli M, Tognoni G, Garattini S (1978) Clinical pharmacokinetics of diazepam. Clin Pharmacokinet 3: 72–91Google Scholar
  12. Pacifici GM, Cuoci L, Placidi GF (1978) Role of the gestational age on the distribution of pinazepam and its metabolite N-desmethyldiazepam in rabbit embryo, fetus and mother. 7th International Congress of Pharmacology, Paris, FranceGoogle Scholar
  13. Pacifici GM, Placidi GF (1981) First pass effect of pinazepam in the rabbit liver. Eur J Drug Metab Pharmacokinet (In press)Google Scholar
  14. Pacific GM, Cuoci L, Placidi GF (1981a) Disposition, distribution and first-pass effect of pinazepam in rats. Drug Metab Dispos (In press)Google Scholar
  15. Pacifici GM, Placidi GF (1977) Rapid and sensitive electron-capture gaschromatographic method for the determination of pinazepam and its metabolites in human plasma urine and milk. J Chromatogr 135: 133–139Google Scholar
  16. Pacifici GM, Cuoci L, Placidi GF, Fornaro P, Gomeni R (1981b) Elimination kinetics of N-desmethyldiazepam in two young and elderly subjects. Eur J Drug Metab Pharmacokinet (In press)Google Scholar
  17. Post C, Lindgren S, Bertler A, Malmgren H (1977) Pharmacokinetics of N-desmethyldiazepam in healthy volunteers after single daily dose of dipotassium Chlorazepate. Psychopharmacology 53: 105–109Google Scholar
  18. Schartz MA, Postma E (1970) Metabolism of flurazepam, a benzodiazepine, in man and dog. J Pharm Sci 59: 1800–1806Google Scholar
  19. Scrollini F, Caliari S, Romano P, Torchio P (1975) Toxicological and pharmacological investigations of pinazepam (7-Chloro-1-propargyl-5-phenyl-3H-1,4-benzodiazepin-2-one) a new psychotherapeutic agent. Arzneim Forsch 25:934–940Google Scholar
  20. Scrollini F, Pizzi A, Amigoni S (1978) The psychopharmacological properties of pinazepam, a new benzodiazepine derivative. Arzneim Forsch 28:423–426Google Scholar
  21. Smith MT, Evans LEJ, Eadie MJ, Tyrer JH (1979) Pharmacokinetics of prazepam in man. Eur J Clin Pharmacol 16:141–147Google Scholar
  22. Tansella M, Burti L, Siciliani O, Zimmerman C, Schiavon M, Gerna M, Tognoni G, Morselli PL (1975) N-desmethyldiazepam and amylobarbitone sodium as hypnotics in anxions patients. Plasma levels, Clinical efficacy and residual effects. Psychopharmacologia 41:81–85Google Scholar
  23. Tognoni G, Gomeni R, De Maio D, Alberti GG, Franciosi P, Scieghi G (1975) Pharmacokinetics of N-desmethyldiazepam in patients suffering from insomnia and treated with nortriptyline. Br J Clin Pharmacol 2:227–232Google Scholar
  24. Tosi GC, Tosi GC, Hattab JR (1973) The use of N-desmethyldiazepam in out patients suffering from insomnia. Curr Ther Res 15:460–464Google Scholar
  25. Trebbi A, Gervasi GB, Comi V (1975) Determination of pinazepam and its metabolites in serum, urine and brain of animals and man by gaschromatography and mass spectrometry. J Chromatogr 110:309–319Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • G. M. Pacifici
    • 1
  • G. F. Placidi
    • 2
  • P. Fornaro
    • 2
  • R. Gomeni
    • 3
  1. 1.Istituto di Patologia GeneraleUniversity of PisaPisaItaly
  2. 2.Clinica Psichiatrica, Medical SchoolUniversity of PisaPisaItaly
  3. 3.Department of Clinical ResearchStatistics and Pharmacokinetics Unit, Synthelabo-LersParisFrance

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