Skip to main content
PMC home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1985 Jan;19(1):95–98. doi: 10.1111/j.1365-2125.1985.tb02619.x

Flunitrazepam and lormetazepam do not affect the pharmacokinetics of the benzodiazepine antagonist Ro 15-1788.

U Klotz, T Duka, R Dorow, A Doenicke
PMCID: PMC1463785  PMID: 3919752

Abstract

Following a single intravenous dose of 0.1 mg/kg, the pharmacokinetics of Ro 15-1788, a specific benzodiazepine antagonist, have been investigated in 20 healthy male volunteers. In random order injection of Ro 15-1788 has been preceded (5 min) by intravenous dosing with 0.06 mg/kg of lormetazepam (n = 6), 0.03 mg/kg of flunitrazepam (n = 8) or placebo (n = 6). The rapid elimination of the antagonist could be characterized by an elimination half-life between 0.9 to 1.4 h and a total plasma clearance of 727 to 1440 ml/min. These single dose studies indicate that the disposition of Ro 15-1788 was not affected by the acute coadministration of both benzodiazepines.

Full text

PDF
95

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allonen H., Ziegler G., Klotz U. Midazolam kinetics. Clin Pharmacol Ther. 1981 Nov;30(5):653–661. doi: 10.1038/clpt.1981.217. [DOI] [PubMed] [Google Scholar]
  2. Arvidsson S. B., Ekström-Jodal B., Martinell S. A., Niemand D. Aminophylline antagonises diazepam sedation. Lancet. 1982 Dec 25;2(8313):1467–1467. doi: 10.1016/s0140-6736(82)91373-3. [DOI] [PubMed] [Google Scholar]
  3. Avant G. R., Speeg K. V., Jr, Freemon F. R., Schenker S., Berman M. L. Physostigmine reversal of diazepam-induced hypnosis. A study in human volunteers. Ann Intern Med. 1979 Jul;91(1):53–55. doi: 10.7326/0003-4819-91-1-53. [DOI] [PubMed] [Google Scholar]
  4. Darragh A., Lambe R., Kenny M., Brick I., Taaffe W., O'Boyle C. RO 15-1788 antagonises the central effects of diazepam in man without altering diazepam bioavailability. Br J Clin Pharmacol. 1982 Nov;14(5):677–682. doi: 10.1111/j.1365-2125.1982.tb04956.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Darragh A., Lambe R., Scully M., Brick I., O'Boyle C., Downe W. W. Investigation in man of the efficacy of a benzodiazepine antagonist, Ro 15-1788. Lancet. 1981 Jul 4;2(8236):8–10. doi: 10.1016/s0140-6736(81)90251-8. [DOI] [PubMed] [Google Scholar]
  6. Doenicke A., Kugler J., Kropp M., Laub M., Kalbfleisch G. Der hypnotische Effekt des neuen Benzodiazepinderivates Lormetazepam nach intravenöser Injektion. Anaesthesist. 1979 Dec;28(12):578–583. [PubMed] [Google Scholar]
  7. Gaillard J. M., Blois R. Effect of the benzodiazepine antagonist Ro 15-1788 on flunitrazepam-induced sleep changes. Br J Clin Pharmacol. 1983 May;15(5):529–536. doi: 10.1111/j.1365-2125.1983.tb02086.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Grote B., Doenicke A., Kugler J., Laub M., Ott H., Fichte K., Suttmann H., Zwisler P. Die antagonistische Wirkung von Physostigmin auf die Sedierung durch Lormetazepam. Anaesthesist. 1981 Dec;30(12):627–632. [PubMed] [Google Scholar]
  9. Henauer S. A., Hollister L. E., Gillespie H. K., Moore F. Theophylline antagonizes diazepam-induced psychomotor impairment. Eur J Clin Pharmacol. 1983;25(6):743–747. doi: 10.1007/BF00542513. [DOI] [PubMed] [Google Scholar]
  10. Kanto J., Klotz U. Intravenous benzodiazepines as anaesthetic agents: pharmacokinetics and clinical consequences. Acta Anaesthesiol Scand. 1982 Dec;26(6):554–569. doi: 10.1111/j.1399-6576.1982.tb01817.x. [DOI] [PubMed] [Google Scholar]
  11. Klotz U., Ziegler G., Reimann I. W. Pharmacokinetics of the selective benzodiazepine antagonist Ro 15-1788 in man. Eur J Clin Pharmacol. 1984;27(1):115–117. [PubMed] [Google Scholar]
  12. Morgan P. F., Stone T. W. Structure-activity studies on the potentiation of benzodiazepine receptor binding by ethylenediamine analogues and derivatives. Br J Pharmacol. 1983 Aug;79(4):973–977. doi: 10.1111/j.1476-5381.1983.tb10543.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Pandit U. A., Kothary S. P., Samra S. K., Domino E. F., Pandit S. K. Physostigmine fails to reverse clinical, psychomotor, or EEG effects of lorazepam. Anesth Analg. 1983 Jul;62(7):679–685. [PubMed] [Google Scholar]
  14. Rapold H. J., Follath F., Scollo-Lavizzari G., Kehl O., Ritz R. Verlängertes Koma durch Sedation mit Diazepam bei beatmeten Patienten. Diagnostische und therapeutische Anwendung des Benzodiazepin-Antagonisten Ro 15-1788. Dtsch Med Wochenschr. 1984 Mar 2;109(9):340–344. doi: 10.1055/s-2008-1069192. [DOI] [PubMed] [Google Scholar]
  15. Stovner J., Endresen R., Osterud A. Intravenous anaesthesia with a new benzodiazepine Ro 5-4200. Acta Anaesthesiol Scand. 1973;17(3):163–169. doi: 10.1111/j.1399-6576.1973.tb00813.x. [DOI] [PubMed] [Google Scholar]
  16. Timm U., Zell M. Determination of the benzodiazepine antagonist Ro 15-1788 in plasma by high-performance liquid chromatography with UV detection. Arzneimittelforschung. 1983;33(3):358–362. [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES