Summary
A method is described for the assay of therapeutic levels of butobarbital (5-ethyl-5-n-butylbarbituric acid) in human plasma, which involves a single extraction step followed by gas chromatography with alkali flame ionization detection. The pharmacokinetics of butobarbital were studied in five healthy volunteers after oral administration of 200 mg. Plasma concentrations were determined at regular intervals up to 96 h and the data were fitted by non-linear, least squares regression analysis according to one-compartment kinetics. The average lag time was 0.11 h and the absorption half-life 0.21 h. The elimination half-life varied from 33.6 to 41.5 h with an average of 37.5 h. Four of the volunteers participated in a study of multiple dosing (every 24 h) during which substantial accumulation of butobarbital was observed. The elimination half-life after termination of drug administration had decreased to about 20–25% of its initial value, probably because of enzyme induction. It was concluded that butobarbital could not be regarded as a suitable drug for treatment of insomnia, since CNS depressant effects were likely to persist into the following day. Repeated administration of butobarbital should be avoided and its incidental use restricted to patients who require day-time sedation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Balasubramaniam, K., Lucas, S.B., Mawer, G.E., Simons, P.J.: The kinetics of amylobarbitone metabolism in healthy men and women. Brit. J. Pharmacol.39, 564–572 (1970)
Bond, A.J., Lader, M.H.: Residual effects of hypnotics. Psychopharmacologia (Berl.)25, 117–132 (1972)
Breimer, D.D.: Reclassification of barbiturates according to their pharmacokinetic behaviour in humans. Abstracts 35th International Congress of Pharmaceutical Sciences, Dublin, September 1 – 5, p. 41, 1975a
Breimer, D.D.: Pharmacokinetic and biopharmaceutical aspects of hypnotic drug therapy. Proceedings International Symposium on Clinical Pharmacy and Clinical Pharmacology, Boston, U.S.A., September 1975. Amsterdam: Excerpta Medica in press 1976
Breimer, D.D., van Rossum, J.M.: Rapid and sensitive gas chromatographic determination of hexobarbital in plasma of man using a nitrogen detector. J. Chromatogr.88, 235–243 (1974)
Breimer, D.D., de Boer, A.G.: Pharmacokinetics and relative bioavailability of heptabarbital and heptabarbital sodium after oral administration. Europ. J. clin. Pharmacol.9, 169–178 (1975)
Breimer, D.D., de Boer, A.G.: Pharmacokinetics and relative bioavailability of vinylbital in man after oral and rectal administration. Arzneimittel-Forsch. (Drug Research)26, 448–454 (1976)
Breimer, D.D., Winten, M.A.C.M.: Pharmacokinetics and relative bioavailability of cyclobarbital calcium in man after oral administration. Europ. J. clin. Pharmacol.9, 443–450 (1976)
Breimer, D.D., Honhoff, C., Zilly, W., Richter, E., van Rossum, J.M.: Pharmacokinetics of hexobarbital in man after intravenous infusion. J. Pharmacokin. Biopharm.3, 1–11 (1975)
Butler, T.C., Mahaffee, C., Waddell, W.J.: Phenobarbital: Studies of elimination, accumulation, tolerance and dosage schedules. J. Pharmacol. exp. Ther.111, 425–435 (1954)
Ehrnebo, M.: Pharmacokinetics and distribution properties of pentobarbital in humans following oral and intravenous administration. J. pharm. Sci.63, 1114–1118 (1974)
Gibaldi, M., Perrier, D.: Pharmacokinetics, p. 33. New York: Marcel Dekker 1975
Gilbert, J.N.T., Natunen, T., Powell, J.W., Saunders, L.: A kinetic study of human urinary excretion results for butobarbitone and its metabolites. J. Pharm. Pharmacol.26, Suppl., 16–23 (1974)
Grove, J., Toseland, P.A., Draffan, G.H., Clare, R.A., Williams, F.M.: Butobarbitone metabolism in man: Identification of 3'-ketobutobarbitone. J. Pharm. Pharmacol.26, 175–178 (1974)
Hare, E.H.: Comparative efficacy of hypnotics: A self controlled, selfrecorded clinical trial in neurotic patients. Brit. J. prev. soc. Med.9, 140–146 (1959)
Lodge-Patch, I.C., Eilenberg, M.D., Hare, E.H.: Ethinamate (Valmid) and methyprylone (Noludar) as hypnotics. A comparative trial. J. ment. Sci.106, 1455–1458 (1960)
Mark, L.C.: Archaic classification of barbiturates. Clin. Pharmacol. Ther.10, 287–291 (1969)
Martindale: The Extra Pharmacopoeia, p. 891. London: The Pharmaceutical Press 1972
Parsons, T.W.: Clinical comparison of barbiturates as hypnotics. Brit. med. J.1963 II, 1035–1037
Prescott, L.F., Roscoe, P., Forrest, J.A.H.: Plasma concentrations and drug toxicity in man. In: Biological effects of drugs in relation to their plasma concentrations (eds. D.S. Davies, B.N.C. Prichard), p. 65. London: MacMillan 1973
Remmer, H.: Induction of drug metabolizing enzyme system in the liver. Europ. J. clin. Pharmacol.5, 116–136 (1972)
Rieder, J.: Plasma levels and derived pharmacokinetic characteristics of unchanged nitrazepam in man. Arzneimittel-Forsch. (Drug Research)23, 212–218 (1973)
Riedmann, M.: Gas chromatographic analysis of drugs and drug metabolites in biological samples. Xenobiot.3, 411–434 (1973)
Stewart, J.S.: Clinical trial of methylprylene, a piperidine hypnotic. Brit. med. J.1956 II, 1465–1467
Vree, T.B., Baars, A.M., van der Kleijn, E.: Capacity-limited elimination of 4-hydroxybutyrate (Gamma-OH), ethanol and vinylbital (Bykonox). Pharm. Weekblad110, 1257–1262 (1975)
Zelvelder, W.G.: Therapeutic evaluation of hypnotics. Assen: Van Gorcum 1971
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Breimer, D.D. Pharmacokinetics of butobarbital after single and multiple oral doses in man. Eur J Clin Pharmacol 10, 263–271 (1976). https://doi.org/10.1007/BF00558339
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00558339