Skip to main content

Clinical Pharmacokinetics of Nitrazepam

Summary

Nitrazepam is one of the oldest benzodiazepines and is widely used as an hypnotic throughout the world, except North America, where it is not available. It is a safe hypnotic, with low acute toxicity and minor side effects. Development of tolerance or dependence and withdrawal symptoms are rare and very few known interactions with other drugs exist.

The absorption of nitrazepam from the gastrointestinal tract is fairly rapid (tmax ranging 0.5 to 7 hours). The bioavailability after oral intake averages about 80%. Maximum plasma concentrations after a single 5mg dose are of the order of 40ng/ml. As a lipophilic drug, nitrazepam is distributed rapidly in the body. The plasma levels can be fitted to a 2-compartment open model. The α-phase is rather rapid and the elimination phase is characterised by a long half-life of about 30 hours; accumulation with daily use therefore occurs. Marked interindividual variation (up to 10-fold) is found in all pharmacokinetic parameters. Age and immobilising diseases may influence the parameters, evidently increasing Vdβ and t1/2β

A similar amount of protein-free drug found in the plasma, i.e. 10 to 15% of the total plasma level, is found in the cerebrospinal fluid. In saliva the concentrations are significantly smaller. Nitrazepam penetrates the human placenta. In early pregnancy, the ratio of cord to maternal plasma concentration is about 0.5, 12 hours after drug administration. In late pregnancy, the ratio reaches 1 within a few hours. Breast milk concentrations are about one-half of those in maternal plasma.

Nitrazepam has no clinically active metabolites. It is excreted mainly as conjugated and non-conjugated 7-aminonitrazepam and 7-acetamidonitrazepam. Polymorphic acetylation is not likely to be of clinical importance. Enzyme induction or significant loss of efficacy have not been found with long term use.

There is no significant correlation between plasma concentrations and clinical effects (or side effects) of nitrazepam. Plasma level monitoring is therefore of no benefit clinically (except for special cases, e.g. in epileptic patients). Increased responsiveness in terms of therapeutic effects and side effects is evident in the elderly. Therefore, small doses not exceeding 5mg daily should be prescribed for geriatric patients.

This is a preview of subscription content, access via your institution.

References

  • Adam, K.; Adamson, L.; Brezinova, V.; Hunter, W. and Oswald, I.: Nitrazepam: lastingly effective but trouble on withdrawal. British Medical Journal 1: 1558–1560 (1976a).

    PubMed  CAS  Article  Google Scholar 

  • Adam, K.; Adamson, L. and Oswald, I.: Subjective ratings of sleep quality and anxiety after placebo, drug and a food drink. Postgraduate Medical Journal 52: 42–43 (1976b).

    PubMed  CAS  Article  Google Scholar 

  • Adams, R.G.: Pre-sleep ingestion of two hypnotic drugs and subsequent performance. Psychopharmacologia (Berlin) 40: 185–190 (1974).

    CAS  Article  Google Scholar 

  • Amrein, R.; Cano, J.P.; Hartmann, D.; Ziegler, W.H. and Dubuis, R.: Clinical and psychometric effects of flunitrazepam observed during the day in relation to pharmacokinetic data; in Priest et al. (Eds) Sleep Research, Proceedings of the Northern European Symposium on Sleep Research, Basle, September 26 and 27, 1978, pp.83–98 (MTP Press, Lancaster 1979).

    Google Scholar 

  • Andersen, T. and Lingjaerde, O.: Nitrazepam as sleep-inducing agent. British Journal of Psychiatry 115: 1393–1397 (1969).

    PubMed  CAS  Article  Google Scholar 

  • Ballinger, B.R.; Presly, A.; Reid, A.H. and Stevenson, I.H.: The effects of hypnotics on imipramine treatment. Psychopharmacologia (Berlin) 39: 267–274 (1974).

    CAS  Article  Google Scholar 

  • Beharrel, G.P.; Hailey, D.M. and McLaurin, M.K.: Determination of nitrazepam (Mogadon) in plasma by electron capture gas-liquid chromatography. Journal of Chromatography 70: 45–52 (1973).

    Google Scholar 

  • Bellantuono, C.; Reggi, V.; Tognoni, G. and Garattini, S.: Benzodiazepines: Clinical Pharmacology and Therapeutic Use. Drugs 19: 195–219 (1980).

    PubMed  CAS  Article  Google Scholar 

  • Beyer, K.-H. von and Sadée, W.; Spectrophotometrische Bestimmung von 5-phenyl-1,4-benzodiazepine Derivaten und Untersuchungen über den Metabolismus des Nitrazepam. Arzneimittel-Forschung 19: 1929–1931 (1969).

    PubMed  CAS  Google Scholar 

  • de Boer, A.G.; Röst-Kaiser, J.; Bracht, H. and Breimer, D.D.: Assay of underivatized nitrazepam and clonazepam in plasma by capillary gas chromatography applied to pharmacokinetic and bioavailability studies in humans. Journal of Chromatography 145: 105–114 (1978).

    PubMed  Article  Google Scholar 

  • Bond, A.J. and Lader, M.H.: Residual effects of hypnotics. Psychopharmacologia (Berlin) 25: 117–132 (1972).

    CAS  Article  Google Scholar 

  • Borland, R.G. and Nicholson, A.N.: Comparison of the residual effects of two benzodiazepines (nitrazepam and nitrazepam hydrochloride) and pentobarbitone sodium on human performance. British Journal of Clinical Pharmacology 2: 9–17 (1975).

    PubMed  CAS  Google Scholar 

  • Breimer, D.D.: Clinical Pharmacokinetics of hypnotics. Clinical Pharmacokinetics 2: 93–109 (1977).

    PubMed  CAS  Article  Google Scholar 

  • Breimer, D.D.; Bracht, H. and de Boer, A.G.: Plasma level profile of nitrazepam (Mogadon®) following oral administration (corresp). British Journal of Clinical Pharmacology 4: 709–711 (1977).

    CAS  Article  Google Scholar 

  • Breimer, D.D.; Jochemsen, R. and von Albert, H.H.: Pharmacokinetics of benzodiazepines; short-acting versus long-acting. Arzneimittel-Forschung 30: 875–881 (1980).

    PubMed  CAS  Google Scholar 

  • Brodersen, P.E. and Mikkelsen, B.O.: Behandling af sevnforstyrrelser med flurazepam (Dalmadorm®), nitrazepam (Mogadon®) og allypropymal. Ugerskrift før Laeger 138: 88–90 (1976).

    CAS  Google Scholar 

  • Brooks, M.A. and Hackman, M.R.: Trace level determination of h4-benzodiazepines in blood by differential pulse polarography. Analytical Chemistry 47: 2059–2062 (1975).

    PubMed  CAS  Article  Google Scholar 

  • Cano, J.P.; Soliva, M.; Hartmann, D.; Ziegler, W.H. and Amrein, R.: Bioavailability from various galenic formulations of flunitrazepam. Arzneimittel-Forschung 27: 2383–2388 (1977).

    PubMed  CAS  Google Scholar 

  • Castleden, C.M.; George, C.F.; Marcer, D. and Hallen, C.: Increased sensitivity to nitrazepam in old age. British Medical Journal 1: 10–12 (1977).

    PubMed  CAS  Article  Google Scholar 

  • Clark, T.J.H.; Collins, J.V. and Tong, D.: Respiratory depression caused by nitrazepam in patients with respiratory failure. Lancet 2: 737–738 (1971).

    PubMed  CAS  Article  Google Scholar 

  • Curry, S.H.; Whelpton, R. and Scott, D.F.: Changes in reaction time and drug plasma concentrations after nitrazepam and glutethimide. British Journal of Clinical Pharmacology 4: 109–114 (1977).

    PubMed  CAS  Article  Google Scholar 

  • Dixon, R.; Lucek, R.; Young, R.; Ning, R. and Darragh, A.: Radioimmunoassay for nitrazepam in plasma. Life Sciences 25: 311–316 (1979).

    PubMed  CAS  Article  Google Scholar 

  • Ehrsson, H. and Tilly, A.: Electron capture gas chromatography of nitrazepam in human plasma as methyl derivative. Analytical Letter 6: 197–202 (1973).

    CAS  Article  Google Scholar 

  • Ellaithy, M.M.; Volke, J. and Manousek, O.: Differential pulse polarography of some benzodiazepines and their determination in urine. Talanta 24: 137–140 (1977).

    PubMed  CAS  Article  Google Scholar 

  • Evans, J.G. and Jarvis, E.H.: Nitrazepam and the elderly. British Medical Journal 4: 487 (1972).

    PubMed  CAS  Article  Google Scholar 

  • Flach, C.: En ny clopoxidum analog (Ro 4.5360) som sovmiddel sammenlignet med allypropymal. Nordisk Median 72: 1071–1075 (1964).

    CAS  Google Scholar 

  • Freuehen, I. and Østergaard, J.; Mogadon et nyt hypnotikum. Ugerskrift før Laeger 128: 142–143 (1966).

    Google Scholar 

  • Freuchen, I.; Østergaard, J. and Mikkelsen, O.: Flunitrazepam (Rohypnol®) compared with nitrazepam (Mogadon®) and aprobarbital as evening premedication prior to anaesthesia: A controlled clinical trial. Current Therapeutic Research 23: 90–93 (1978).

    Google Scholar 

  • Fruensgaard, K. and Vaag, U.H.: Abstinenspsykose efter nitrazepam. Ugerskrift før laeger 137: 633–634 (1975).

    CAS  Google Scholar 

  • Greaves, M.S.: Quantitative determination of medazepam, diazepam and nitrazepam in whole blood by flame-ionization gas-liquid chromatography. Clinical Chemistry 20: 141–147 (1974).

    PubMed  CAS  Google Scholar 

  • Greenblatt, D.J. and Allen, M.D.: Toxicity of nitrazepam in the elderly: A report from the Boston collaborative drug surveillance program. British Journal of Clinical Pharmacology 5: 407–413 (1978).

    PubMed  CAS  Article  Google Scholar 

  • Grundström, R.; Holmberg, G. and Hansen, T.: Degree of sedation obtained with various doses of diazepam and nitrazepam. Acta Pharmacologica et Toxicologica 43: 13–18 (1978).

    PubMed  Article  Google Scholar 

  • Haider, I.: A double-blind controlled trial of a non-barbiturate hypnotic — nitrazepam. Br. J. Psych. 114: 337–343 (1968).

    CAS  Article  Google Scholar 

  • Harenko, A.: A comparison between chlormethiazole and nitrazepam as hypnotics in psycho-geriatric patients. Current Medical Research and Opinion 2: 657–663 (1975).

    CAS  Article  Google Scholar 

  • Hartelius, H.; Larsson, A.K.; Lepp, M.; Malm, U.; Arvidsson, A. and Dahlström, H.: A controlled long-term study of flunitrazepam, nitrazepam and placebo, with special regard to withdrawal effects. Acta Psychiatrica Scandinavica 58: 1–15 (1978).

    PubMed  CAS  Article  Google Scholar 

  • Haslett, W.H.K. and Dundee, J.W.: Studies of drugs given before anaesthesia. XIV: Two benzodiazepine derivatives chlordiazepoxide and diazepam. British Journal of Anaesthesia 40: 250–254 (1968).

    PubMed  CAS  Article  Google Scholar 

  • Hewick, D.S. and Shaw, V.: The importance of the intestinal microflora in nitrazepam metabolism in the rat. British Journal of Pharmacology 62 (Suppl): 427 P (Mar 1978a).

    Google Scholar 

  • Hewick, D.S. and Shaw, V.: Tissue distribution of radioactivity after injection of [14C] Nitrazepam in young and old rats. Journal of Pharmacy and Pharmacology 30: 318–319 (1978b).

    PubMed  CAS  Article  Google Scholar 

  • Hindmarch, I.: A 1,4-benzodiazepine, Temazepam (K 3917), its effect on some psychological parameters of sleep and behaviour. Arzneimittel-Forschung 25: 1836–1839 (1975).

    PubMed  CAS  Google Scholar 

  • Hindmarch, I.: A repeated dose comparison of three benzodiazepine derivatives (nitrazepam, flurazepam and flunitrazepam) on subjective appraisals of sleep and measures of psychomotor performance the morning following night-time medication. Acta Psychiatrica Scandinavica 56: 373–381 (1977).

    PubMed  CAS  Article  Google Scholar 

  • Hossmann, V.; Maling, T.; Reid, J.L. and Dollery, C.T.: Doubleblind placebo controlled, cross-over comparison of the sedative and haemodynamic effect of single doses of Clonidine and nitrazepam. British Journal of Clinical Pharmacology 8 (Suppl.): 401 P(Jul 1979).

    Article  Google Scholar 

  • Hunt, P.; Husson, J.-M. and Raynaud, J.-P.: A radioreceptor assay for benzodiazepines. Journal of Pharmacy and Pharmacology 31: 448–451 (1979).

    PubMed  CAS  Article  Google Scholar 

  • Iisalo, E.; Kangas, L. and Ruikka, I.: Pharmacokinetics of nitrazepam in young volunteers and aged patients. British Journal of Clinical Pharmacology 4 (Suppl.): 646 P (July 1977).

    Article  Google Scholar 

  • James, N. Mcl. and Montague, A.F.: A double blind trial of nitrazepam and flurazepam as sedatives. New Zealand Medical Journal 81: 246–248 (1975).

    PubMed  CAS  Google Scholar 

  • Jeavons, P.M.: Choice of drug therapy in epilepsy. The Practitioner 219: 542–556 (1997).

    Google Scholar 

  • Jones, D.M.; Jones, M.E.L.; Lewis, M.J. and Spriggs, T.L.B.: Drugs and human memory: Effects of low doses of nitrazepam and hyoscine on retention. British Journal of Clinical Pharmacology 7: 479–483 (1979).

    PubMed  CAS  Article  Google Scholar 

  • Kales, A.; Bixler, E.O.; Tan, T.-L; Scharf, M.B. and Kales, J.D.: Chronic hypnotic drug use. Ineffectiveness, drug withdrawal insomnia, and dependence. Journal of the American Medical Association 227: 513–517 (1974).

    PubMed  CAS  Article  Google Scholar 

  • Kales, A.; Scharf, M.G.; Kales, J.D. and Soldatos, C.R.: Rebound insomnia. A potential hazard following withdrawal of certain benzodiazepines. Journal of the American Medical Association 241: 1692–1695 (1979).

    PubMed  CAS  Article  Google Scholar 

  • Kangas, L.: Comparison of two gas-liquid chromatographic methods for the determination of nitrazepam in plasma. Journal of Chromatography 136: 259–270 (1977).

    PubMed  CAS  Article  Google Scholar 

  • Kangas, L.: Determination of nitrazepam and its main metabolites in urine by gas-liquid chromatography: Use of electron capture and nitrogen-selective detectors. Journal of Chromatography 172: 273–278 (1979a).

    PubMed  CAS  Article  Google Scholar 

  • Kangas, L.: Urinary elimination of nitrazepam and its main metabolites. Acta Pharmacologica et Toxicologica 45: 16–19 (1979b).

    PubMed  CAS  Article  Google Scholar 

  • Kangas, L.; Kanto, J. and Erkkola, R.: Transfer of nitrazepam across the human placenta. European Journal of Clinical Pharmacology 12: 355–357 (1977a).

    PubMed  CAS  Article  Google Scholar 

  • Kangas, L.; Kanto, I. and Mansikka, M.: Nitrazepam premedication for minor surgery. British Journal of Anesthesiology 49: 1153–1157 (1977b).

    CAS  Article  Google Scholar 

  • Kangas, L.; Kanto, J.; Siirtola, T. and Pekkarinen, A.: Cerebrospinal fluid concentrations of nitrazepam in man. Acta Pharmacologica et Toxicologica 41: 74–79 (1977c).

    PubMed  CAS  Article  Google Scholar 

  • Kangas, L.; Kanto, J. and Syvälahti, E.: Plasma nitrazepam concentrations after an acute intake and their correlation to sedation and serum growth hormone levels. Acta Pharmacologica et Toxicologica 41: 65–73 (1977d).

    PubMed  CAS  Article  Google Scholar 

  • Kangas, L.; Allonen, H.; Lammintausta, R.; Salonen, M. and Pekkarinen, A.: Pharmacokinetics of nitrazepam in saliva and serum after a single oral dose. Acta Pharmacologica et Toxicologica 45: 20–24 (1979a).

    PubMed  CAS  Article  Google Scholar 

  • Kangas, L.; Iisalo, E.; Kanto, J.; Lehtinen, V.; Pynnönen, S.; Ruikka, I.; Salminen, J.; Sillanpää, M. and Syvälahti, E.: Human pharmacokinetics of nitrazepam: Effect of age and diseases. European Journal of Clinical Pharmacology 15: 163–170 (1979b).

    PubMed  CAS  Article  Google Scholar 

  • Kangas, L.; Kanto, J.; Lehtinen, V. and Salminen, J.: Long term nitrazepam treatment in psychiatric out patients with insomnia. Psychopharmacologia (Berlin) 63: 63–66 (1979c).

    CAS  Article  Google Scholar 

  • Kangas, L.; Kanto, J.; Pakkanen, A. and Mansikka, M.: Comparison of sedatory and anxiolytic properties of placebo, tofisopam and nitrazepam as oral premedicants; in Radouco-Thomas and Garcin (Eds) Progress in Neuro-Psychopharmacology (Suppl.), Abstract of the 12th CINP Congress, Göteborg, Sweden 22–26 June 1980, p. 197 (Pergamon, Gotab. Kungälv 1980).

    Google Scholar 

  • Kanto, J.; Iisalo, E.; Lehtinen, V. and Salminen, J.: The concentrations of diazepam and its metabolites in the plasma after an acute and chronic administration. Psychopharmacologia (Berlin) 36: 123–131 (1974).

    CAS  Article  Google Scholar 

  • Karim, A.K.M.B. and Price Evans, D.A.: Polymorphic acetylation of nitrazepam. Journal of Medical Genetics 13: 17–19 (1976).

    PubMed  CAS  Article  Google Scholar 

  • Kinawi, A. and Teller, C.: Zur Interaktion von Phenprocoumon mit Diazepam und Nitrazepam. Journal of Clinical Chemistry and Clinical Biochemistry 16: 313–314 (1978)

    CAS  Google Scholar 

  • Lahtinen, U.; Lahtinen, A. and Pekkola, P.: The effect of nitrazepam on manual skill, grip strength, and reaction time with special reference to subjective evaluation of effects on sleep. Acta Pharmacologica et Toxicologica 42: 130–134 (1978).

    PubMed  CAS  Article  Google Scholar 

  • Liljequist, R. and Manila, M.J.: Acute effects of temazepam and nitrazepam on psychomotor skills and memory. Acta Pharmacologica et Toxicologica 44: 364–369 (1979).

    PubMed  CAS  Article  Google Scholar 

  • Lingjaerde, O.: Discussion, pan III; in Priest et al. (Eds) Sleep Research, Proceedings of the Northern European Symposium on Sleep Research, Basle, September 26 and 27, 1978 p.216 (MTP Press, Lancaster 1979).

    Google Scholar 

  • Linnoila, M.: Drug interaction on psychomotor skills related to driving. Annates Medicinae Experimentalis et Biologiae Fenniae 51: 118–124 (1973).

    CAS  Google Scholar 

  • Linnoila, M. and Viukari, M.: Efficacy and side effects of nitrazepam and thioridazine as sleeping aids in psychogeriatric inpatients. British Journal of Psychiatry 128: 566–569 (1976).

    PubMed  CAS  Article  Google Scholar 

  • Linnoila, M.; Korttila, K. and Mattila, M.J.: Effect of food and repeated injections on serum diazepam levels. Acta Pharmacologica et Toxicologica 36: 181–186 (1975).

    PubMed  CAS  Article  Google Scholar 

  • Lunde, P.K.M.; Frislid, K. and Hansteen, V.: Disease and acetylation polymorphism. Clinical Pharmacokinetics 2: 182–197 (1977).

    PubMed  CAS  Article  Google Scholar 

  • Mansikka, M.; Kanto, J. and Kangas, L.: Unpublished data( 1980).

  • Matthew, H.; Proudfoot, A.T.; Aitken, R.C.B.; Raeburn, J.A. and Wright, N.: Nitrazepam — a safe hypnotic. British Medical Journal 3: 23–25 (1969).

    PubMed  CAS  Article  Google Scholar 

  • Misra, P.C.: Nitrazepam (Mogadon) dependence. British Journal of Psychiatry 126: 81–82 (1975).

    PubMed  CAS  Article  Google Scholar 

  • Momose, T.; Ishii, S. and Kuge, T.: Controlled comparison of estazolam and nitrazepam as hypnotics on the preoperative night sleep. Current Therapeutic Research 19: 277–291 (1976).

    PubMed  CAS  Google Scholar 

  • Moore, B.; Nickless, G.; Hallett, C. and Howard, A.G.: Analysis of nitrazepam and its metabolites by high-pressure liquid chromatography. Journal of Chromatography 137: 215–217 (1977).

    PubMed  CAS  Article  Google Scholar 

  • Morgan, H.; Scott, D.F. and Joyce, C.R.B.: The effects of four hypnotic drugs and placebo on normal subjects’ sleeping and dreaming at home. British Journal of Psychiatry 117: 649–652 (1970).

    PubMed  CAS  Article  Google Scholar 

  • Mohler, H.; Okada, T.; Heitz, Ph. and Ulrich, J.: Biochemical identification of the site of action of benzodiazepines in human brain by 3H-diazepam binding. Life Sciences 22: 985–996 (1978).

    PubMed  CAS  Article  Google Scholar 

  • Møller-Jensen, K.: Determination of nitrazepam in serum by gas-liquid chromatography. Application in bioavailability studies. Journal of Chromatography 111: 389–396 (1975).

    Article  Google Scholar 

  • Nakazawa, Y.; Kotorii, M.; Oshima, M.; Horikawa, S. and Tachibana, H.: Effects of thienodiazepine derivatives on human sleep as compared to those of benzodiazepine derivatives. Psychopharmacologia (Berlin) 44: 165–171 (1975).

    CAS  Article  Google Scholar 

  • Nayal, S.; Castleden, C.M.; George, C.F. and Marcer, D.: The effect of an hypnotic with a short half-life on hangover effect in old patients. Age and Ageing 7 (Suppl): 50–54 (1978)

    Article  Google Scholar 

  • Ogura, C.; Majima, K.; Nakasawa, K.; Nakamura, I.; Umezawa, Y. and Ueda, H.: Comparative study of the effects of flurazepam and nitrazepam on sleep by 24-hour polygraphy. European Journal of Clinical Pharmacology 13: 413–418 (1978).

    CAS  Article  Google Scholar 

  • Okuma, T.; Hata, N. and Fujii, S.: Differential effects of chlorpromazine. Imipramine, nitrazepam and amobarbital on REM sleep and REM density in man. Folia Psychiatrica et Neurologica Japonica 29: 25–37 (1975).

    PubMed  CAS  Google Scholar 

  • Oswald, I.; Lewis, S.A.; Tagney, J.; Firth, H. and Haider, I.: Benzodiazepines and human sleep; in Garattini et al. (Eds) The Benzodiazepines, pp.613–625 (Raven Press, New York 1973).

    Google Scholar 

  • Peck, A.W.; Adams, R; Bye, C. and Wilkinson, R.T.: Residual effects of hypnotic drugs: Evidence for individual differences on vigilance. Psychopharmacology 47: 213–216 (1976).

    CAS  Article  Google Scholar 

  • Peck, A.W.; Bye, C.E. and Claridge, R.: Differences between light and sound sleepers in the residual effects of nitrazepam. British Journal of Clinical Pharmacology 4: 101–108 (1977).

    PubMed  CAS  Article  Google Scholar 

  • Price Evans, D.A.: Personal discussion (1980).

  • Randall, L.O and Kappell, B.: Pharmacological activity of some benzodiazepines and their metabolites; in Garattini et al. (Eds) The Benzodiazepines, pp.27–51 (Raven Press, New York 1973).

    Google Scholar 

  • Reith, H. and Schäfer, H.: Antiepileptika während Schwangerschaft und Stillzeit. Deutsche Medizinische Wochenschrift 104: 818–823 (1979).

    PubMed  CAS  Article  Google Scholar 

  • Rieder, J.: A fluorimetric method for determining nitrazepam and the sum of its main metabolites in plasma and urine. Arzneimittel-Forschung 23: 207–211 (1973a).

    PubMed  CAS  Google Scholar 

  • Rieder, J.: Plasma levels and derived pharmacokinetic characteristics of unchanged nitrazepam in man. Arzneimittel-Forschung 23: 212–218 (1973b).

    PubMed  CAS  Google Scholar 

  • Rieder, J. and Wendt, G.: Pharmacokinetics and metabolism of the hypnotic nitrazepam; in Garattini et al. (Eds) The Benzodiazepines, pp.99–127 (Raven Press, New York 1973).

    Google Scholar 

  • Risberg, A.-M.; Henricsson, S. and Ingvar, D.H.: Evaluation of the effect of fosazepam (a new benzodiazepine), nitrazepam and placebo on sleep patterns in normal subjects. European Journal of Clinical Pharmacology 12: 105–109 (1977).

    PubMed  CAS  Article  Google Scholar 

  • Roden, S.; Harvey, P. and Mitchard, M.: The influence of alcohol on the persistent effects on human performance of the hypnotics Mandrax and nitrazepam. International Journal of Clinical Pharmacology 15: 350–355 (1977).

    CAS  Google Scholar 

  • Rudolf, M.; Geddes, D.M.; Turner, J.A.McM. and Saunders, K.B.: Depression of central respiratory drive by nitrazepam. Thorax 33: 97–100 (1978).

    PubMed  CAS  Article  Google Scholar 

  • Saario, I.; Linnoila, M. and Mäki, M.: Interaction of drugs with alcohol on human psychomotor skills related to driving: Effect of sleep deprivation or two weeks’ treatment with hypnotics. Journal of Clinical Pharmacology 15: 52–59 (1975).

    CAS  Google Scholar 

  • Scheffner, D.: Klinik und Therapie der Epilepsien im Kindersalter Medizinische Welt 26: 494–499 (1975).

    PubMed  CAS  Google Scholar 

  • de Silva, J.A.F.: Choice of sensitivity and specificity in the analysis of drugs in biological fluids: Use of electron capture GLC, spectrophotometry, differential pulse polarography, and radioimmunoassay in the analysis of 1,4-benzodiazepines, in Kellaway and Petersen (Eds) Quantitative Analytic Studies in Epilepsy, pp.11–38 (Raven Press, New York 1976).

    Google Scholar 

  • Sjoqvist, F.; Borgå, O. and Orme, M.L’E.: Fundamentals of clinical pharmacology; in Avery (Ed.) Drug Treatment: Principles and Practice of Clinical Pharmacology and Therapeutics, 2nd ed pp.1–61 (ADIS Press, Netley 1980).

    Google Scholar 

  • Skellern, G.C.; Meier, J.; Knight, B.I. and Whiting, B.: The application of HPLC to the determination of some 1,4-benzodiazepines and their metabolites in plasma. British Journal of Clinical Pharmacology 5: 483–487 (1978).

    PubMed  CAS  Article  Google Scholar 

  • Soldatos, C.R. and Kales, A.: Role of sleep laboratory in the evaluation of hypnotic drugs; in Priest et al. (Eds) Sleep Research, Proceedings of the Northern European Symposium on Sleep Research, Basle, September 26 and 27, 1978, pp.83–98 (MTP Press, Lancaster 1979).

    Google Scholar 

  • Speight, A.N.P.: Floppy-infant syndrome and maternal diazepam and/or nitrazepam. Lancet 2: 878 (1977).

    PubMed  CAS  Article  Google Scholar 

  • Squires, R.F. and Baestrup, C.; Benzodiazepine receptors in rat brain. Nature 266: 732–734 (1977).

    PubMed  CAS  Article  Google Scholar 

  • Swift, C.G.; Hewick, D.S.; Ogg, G. and Stevenson, I.H.: Acetylator phenotype, nitrazepam plasma concentrations and residual effects. British Journal of Clinical Pharmacology 9: 312P–313P (1980).

    Article  Google Scholar 

  • Torry, J.M.: A case of suicide with nitrazepam and alcohol. Practitioner 217: 648–649 (1976).

    PubMed  CAS  Google Scholar 

  • Viukari, M.; Linnoila, M. and Aalto, U.: Efficacy and side effects of flurazepam, fosazepam and nitrazepam as sleeping aids in psychogeriatric patients. Acta Psychiatrica Scandinavica 57: 27–35 (1978).

    PubMed  CAS  Article  Google Scholar 

  • Wickstrøm, E.: Comparative studies with hypnotics; in Priest et al. (Eds) Sleep Research, Proceedings of the Northern Europeaan Symposium on Sleep Research. Basle, September 26 and 27, 1978, pp.155–169 (MTP Press, Lancaster 1979).

    Google Scholar 

  • Yanagi, Y.; Haga, F.; Endo, M. and Kitagawa, S.: Comparative metabolic study of nimetazepam and its desmethyl derivative (nitrazepam) in rats. Xenobiotica 5: 245–257 (1975).

    PubMed  CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kangas, L., Breimer, D.D. Clinical Pharmacokinetics of Nitrazepam. Clin Pharmacokinet 6, 346–366 (1981). https://doi.org/10.2165/00003088-198106050-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-198106050-00002

Keywords

  • Flunitrazepam
  • Maternal Plasma
  • Nitrazepam
  • Flurazepam
  • Hypnotic Drug